NM_001297.5(CNGB1):c.3150del (p.Phe1051fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 8, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000360125.7

Allele description [Variation Report for NM_001297.5(CNGB1):c.3150del (p.Phe1051fs)]

NM_001297.5(CNGB1):c.3150del (p.Phe1051fs)

Gene:

CNGB1:cyclic nucleotide gated channel subunit beta 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16q21

Genomic location:

Preferred name:

NM_001297.5(CNGB1):c.3150del (p.Phe1051fs)

HGVS:

NC_000016.10:g.57897491del
NG_016351.1:g.78628del
NM_001286130.2:c.3132del
NM_001297.5:c.3150delMANE SELECT
NP_001273059.1:p.Phe1045fs
NP_001288.3:p.Phe1051fs
NC_000016.9:g.57931393del
NC_000016.9:g.57931395del
NM_001297.4:c.3150del
NM_001297.4:c.3150delG

Protein change:

F1045fs

Links:

dbSNP: rs753353134

NCBI 1000 Genomes Browser:

rs753353134

Molecular consequence:

NM_001286130.2:c.3132del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001297.5:c.3150del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000330023	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Nov 21, 2017)	germline	clinical testing	Citation Link,
SCV001221515	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 8, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15557452, 24043777, 29202463, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000330023

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Nov 21, 2017)

germline

clinical testing

Citation Link,

SCV001221515

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 8, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers.

Kondo H, Qin M, Mizota A, Kondo M, Hayashi H, Hayashi K, Oshima K, Tahira T, Hayashi K.

Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4433-9.

PubMed [citation]

PMID:: 15557452

Whole genome sequencing in patients with retinitis pigmentosa reveals pathogenic DNA structural changes and NEK2 as a new disease gene.

Nishiguchi KM, Tearle RG, Liu YP, Oh EC, Miyake N, Benaglio P, Harper S, Koskiniemi-Kuendig H, Venturini G, Sharon D, Koenekoop RK, Nakamura M, Kondo M, Ueno S, Yasuma TR, Beckmann JS, Ikegawa S, Matsumoto N, Terasaki H, Berson EL, Katsanis N, Rivolta C.

Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16139-44. doi: 10.1073/pnas.1308243110. Epub 2013 Sep 16.

PubMed [citation]

PMID:: 24043777
PMCID:: PMC3791719

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000330023.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The c.3150delG pathogenic variant in the CNGB1 gene has been reported previously in the compound heterozygous state in a Hispanic female with retinitis pigmentosa (Nishiguchi et al., 2013). The c.3150delG variant causes a frameshift starting with codon Phenylalanine 1051, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 12 of the new reading frame, denoted p.Phe1051LeufsX12. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.3150delG variant was not observed in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.3150delG as a pathogenic variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV001221515.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Phe1051Leufs*12) in the CNGB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CNGB1 are known to be pathogenic (PMID: 15557452, 24043777). This variant is present in population databases (rs753353134, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 24043777, 29202463). It has also been observed to segregate with disease in related individuals. This variant is also known as p.G1050fs. ClinVar contains an entry for this variant (Variation ID: 280141). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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