VCV001328141.15 - ClinVar

NR_023317.1(RNU7-1):n.28C>G

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Likely pathogenic

4 out of 4 submissions contributed to this classification

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NR_023317.1(RNU7-1):n.28C>G

Variation ID: 1328141 Accession: VCV001328141.15

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 12p13.31 12: 6943843 (GRCh38) [ NCBI UCSC ] 12: 7053006 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Dec 18, 2021	Jul 13, 2025	Jan 27, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001301834.1:c.-16+181C>G		intron variant
NM_001301836.2:c.13+181C>G		intron variant
NM_001301837.1:c.-279C>G
NM_001301838.1:c.-480C>G
NM_138425.3:c.-279C>G
NR_023317.1:n.28C>G		non-coding transcript variant
NR_126035.1:n.27C>G
NC_000012.12:g.6943843C>G
NC_000012.11:g.7053006C>G
NG_008047.1:g.24381C>G
NG_008047.2:g.24386C>G
NG_034262.1:g.5027C>G
NG_125067.2:g.114C>G

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000012.12:6943842:C:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA232435235 dbSNP: rs180837208 VarSome

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
Gene	OMIM	HI score Help 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.
C12orf57		-	-	GRCh38 GRCh37	250	330
RNU7-1		-	-	GRCh38	1	41

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.
Aicardi-Goutieres syndrome 9	Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jan 27, 2025	RCV001795577.15
not provided	Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jul 1, 2024	RCV004598147.9

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.
Likely pathogenic (Jul 28, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ICSLVariantClassificationCriteria RUGD 01 April 2020) Method: clinical testing	Aicardi-Goutieres syndrome 9 Affected status: unknown Allele origin: unknown	Illumina Laboratory Services, Illumina Accession: SCV002034789.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021	Publications: PubMed (2) PubMed: 16547514‚ 33230297 Comment: The RNU7-1 n.28C>G variant is a non-protein coding variant that has not been reported in the peer-reviewed literature. However, a different nucleotide change at the … (more) The RNU7-1 n.28C>G variant is a non-protein coding variant that has not been reported in the peer-reviewed literature. However, a different nucleotide change at the same position, n.28C>T, has been reported in at least six individuals with Aicardi-Goutieres syndrome and elevated levels of interferon (Uggenti et al. 2020); in two of these individuals, the n.28C>T variant was confirmed in trans with the n.40_47del variant. The n.28C>G variant is reported at a frequency of 0.000196 in the Latino/Admixed American population of the Genome Aggregation Database (version 3.1.1), a frequency that is consistent with a rare autosomal recessive disorder. Nucleotide 28 is a key position of the sm-binding site, and functional studies have shown that the n.28C>G nucleotide substitution inhibits the assembly and processing efficiency of the U7 snRNP (Kolev and Steiz 2006). Based on the evidence, the n.28C>G variant is classified as likely pathogenic for Aicardi-Goutieres syndrome. (less)

Likely pathogenic (Jan 29, 2024) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV005333357.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: Observed with a second RNU7-1 variant in a patient with nystagmus, microcephaly, and dystonia, but it is not known whether the variants occurred on the … (more) Observed with a second RNU7-1 variant in a patient with nystagmus, microcephaly, and dystonia, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (PMID: 37171742); Published functional studies demonstrate severely impaired RNU7-1 function (PMID: 16547514); Also known as n.28C>G; This variant is associated with the following publications: (PMID: 16547514, 33230297, 37171742) (less)

Likely pathogenic (Jan 27, 2025) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Aicardi-Goutieres syndrome 9 Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV005887048.2 First in ClinVar: Mar 16, 2025 Last updated: May 25, 2025	Publications: PubMed (2) PubMed: 37171742‚ 16547514 Comment: Variant summary: RNU7-1 n.28C>G alters a nucleotide in the non-coding RNA. The variant allele was found at a frequency of 6.9e-05 in 888472 control chromosomes … (more) Variant summary: RNU7-1 n.28C>G alters a nucleotide in the non-coding RNA. The variant allele was found at a frequency of 6.9e-05 in 888472 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in RNU7-1 causing Aicardi-Goutieres syndrome 9 (6.9e-05 vs 0.0011), allowing no conclusion about variant significance. n.28C>G has been reported in the literature in at least one individual affected with Aicardi-Goutieres syndrome (example: Louise Frmond_2023). In functional studies the variant demonstrated impaired RNU7-1 function (Kolev_2006). The following publications have been ascertained in the context of this evaluation (PMID: 16547514, 37171742). ClinVar contains an entry for this variant (Variation ID: 1328141). Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)

Likely pathogenic (Jul 01, 2024) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV005092545.9 First in ClinVar: Aug 04, 2024 Last updated: Jul 13, 2025	Comment: RNU7-1: PM3:Strong, PM2, PS1:Supporting Number of individuals with the variant: 1

Comment:

The RNU7-1 n.28C>G variant is a non-protein coding variant that has not been reported in the peer-reviewed literature. However, a different nucleotide change at the same position, n.28C>T, has been reported in at least six individuals with Aicardi-Goutieres syndrome and elevated levels of interferon (Uggenti et al. 2020); in two of these individuals, the n.28C>T variant was confirmed in trans with the n.40_47del variant. The n.28C>G variant is reported at a frequency of 0.000196 in the Latino/Admixed American population of the Genome Aggregation Database (version 3.1.1), a frequency that is consistent with a rare autosomal recessive disorder. Nucleotide 28 is a key position of the sm-binding site, and functional studies have shown that the n.28C>G nucleotide substitution inhibits the assembly and processing efficiency of the U7 snRNP (Kolev and Steiz 2006). Based on the evidence, the n.28C>G variant is classified as likely pathogenic for Aicardi-Goutieres syndrome.

Comment:

Observed with a second RNU7-1 variant in a patient with nystagmus, microcephaly, and dystonia, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (PMID: 37171742); Published functional studies demonstrate severely impaired RNU7-1 function (PMID: 16547514); Also known as n.28C>G; This variant is associated with the following publications: (PMID: 16547514, 33230297, 37171742)

Comment:

Variant summary: RNU7-1 n.28C>G alters a nucleotide in the non-coding RNA. The variant allele was found at a frequency of 6.9e-05 in 888472 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in RNU7-1 causing Aicardi-Goutieres syndrome 9 (6.9e-05 vs 0.0011), allowing no conclusion about variant significance. n.28C>G has been reported in the literature in at least one individual affected with Aicardi-Goutieres syndrome (example: Louise Frmond_2023). In functional studies the variant demonstrated impaired RNU7-1 function (Kolev_2006). The following publications have been ascertained in the context of this evaluation (PMID: 16547514, 37171742). ClinVar contains an entry for this variant (Variation ID: 1328141). Based on the evidence outlined above, the variant was classified as likely pathogenic.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
JAK Inhibition in Aicardi-Goutières Syndrome: a Monocentric Multidisciplinary Real-World Approach Study.	Frémond ML	Journal of clinical immunology	2023	PMID: 37171742
cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing.	Uggenti C	Nature genetics	2020	PMID: 33230297
In vivo assembly of functional U7 snRNP requires RNA backbone flexibility within the Sm-binding site.	Kolev NG	Nature structural & molecular biology	2006	PMID: 16547514

Text-mined citations for rs180837208 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 13, 2025

ClinVar Genomic variation as it relates to human health

NR_023317.1(RNU7-1):n.28C>G

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs180837208 ...