ClinVar Genomic variation as it relates to human health
NM_005045.4(RELN):c.3477C>A (p.Asn1159Lys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_005045.4(RELN):c.3477C>A (p.Asn1159Lys)
Variation ID: 281243 Accession: VCV000281243.48
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q22.1 7: 103596518 (GRCh38) [ NCBI UCSC ] 7: 103236965 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Aug 27, 2017 Apr 15, 2024 Jan 27, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_005045.4:c.3477C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005036.2:p.Asn1159Lys missense NM_173054.3:c.3477C>A NP_774959.1:p.Asn1159Lys missense NC_000007.14:g.103596518G>T NC_000007.13:g.103236965G>T NG_011877.2:g.397999C>A - Protein change
- N1159K
- Other names
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- Canonical SPDI
- NC_000007.14:103596517:G:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00100 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00100
The Genome Aggregation Database (gnomAD) 0.00140
1000 Genomes Project 30x 0.00141
Trans-Omics for Precision Medicine (TOPMed) 0.00149
The Genome Aggregation Database (gnomAD), exomes 0.00163
Exome Aggregation Consortium (ExAC) 0.00172
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00238
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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RELN | No evidence available | No evidence available |
GRCh38 GRCh37 |
2663 | 3482 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Feb 11, 2020 | RCV000307965.13 | |
Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Nov 1, 2023 | RCV000540494.26 | |
Pathogenic (1) |
no assertion criteria provided
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Jan 1, 2017 | RCV000656002.4 | |
Benign (1) |
criteria provided, single submitter
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Apr 28, 2017 | RCV001161946.6 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 27, 2024 | RCV001085073.9 | |
Likely benign (1) |
criteria provided, single submitter
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Nov 17, 2022 | RCV003977725.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely benign
(Sep 18, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000596763.1
First in ClinVar: Aug 27, 2017 Last updated: Aug 27, 2017 |
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Likely benign
(Sep 04, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000331874.4
First in ClinVar: Dec 06, 2016 Last updated: Apr 09, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Benign
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Norman-Roberts syndrome
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001323867.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
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Benign
(Feb 11, 2020)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics Inc
Accession: SCV000614865.3
First in ClinVar: Aug 27, 2017 Last updated: Jan 26, 2021 |
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Likely benign
(Jan 25, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000565486.3
First in ClinVar: Dec 06, 2016 Last updated: Apr 09, 2018 |
Comment:
This variant is associated with the following publications: (PMID: 14593429, 14515139, 29358611, 32560555)
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Likely benign
(Jan 27, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial temporal lobe epilepsy 7
Norman-Roberts syndrome
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000656285.9
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
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Likely benign
(Nov 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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RELN-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004791204.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Likely benign
(Nov 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001155205.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Comment:
RELN: BS2
Number of individuals with the variant: 13
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Pathogenic
(Jan 01, 2017)
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no assertion criteria provided
Method: case-control
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Childhood epilepsy with centrotemporal spikes
Affected status: yes
Allele origin:
germline
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Bioinformatics Core, Luxembourg Center for Systems Biomedicine
Study: EUROEPINOMICS COGIE
Accession: SCV000588278.1 First in ClinVar: Jun 01, 2018 Last updated: Jun 01, 2018 |
Comment:
CAADphred>15
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001553126.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The RELN p.Asn1159Lys variant was identified in the literature in two sisters affected with autism (Bonora_2013_PMID:14515139). The variant was identified in dbSNP (ID: rs114684479), LOVD … (more)
The RELN p.Asn1159Lys variant was identified in the literature in two sisters affected with autism (Bonora_2013_PMID:14515139). The variant was identified in dbSNP (ID: rs114684479), LOVD 3.0 and ClinVar (classified as likely benign by GeneDx, Invitae, EGL Genetic Diagnostics and Genetic Services Laboratory, University of Chicago, as uncertain significance by Athena Diagnostics Inc and as pathogenic by Bioinformatics Core, Luxembourg Center for Systems Biomedicine). The variant was identified in control databases in 441 of 282460 chromosomes (2 homozygous) at a frequency of 0.001561 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Ashkenazi Jewish in 41 of 10358 chromosomes (freq: 0.003958), European (non-Finnish) in 286 of 128856 chromosomes (freq: 0.00222), South Asian in 55 of 30614 chromosomes (freq: 0.001797), Other in 12 of 7208 chromosomes (freq: 0.001665), Latino in 34 of 35392 chromosomes (freq: 0.000961), African in 10 of 24966 chromosomes (freq: 0.000401) and European (Finnish) in 3 of 25122 chromosomes (freq: 0.000119), but was not observed in the East Asian population. The p.Asn1159 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy. | Bobbili DR | European journal of human genetics : EJHG | 2018 | PMID: 29358611 |
Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP-GEFII gene. | Bacchelli E | Molecular psychiatry | 2003 | PMID: 14593429 |
Analysis of reelin as a candidate gene for autism. | Bonora E | Molecular psychiatry | 2003 | PMID: 14515139 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RELN | - | - | - | - |
Text-mined citations for rs114684479 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.