Variant 16-57959985-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_001297.5(CNGB1):c.664C>T(p.Gln222Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CNGB1
NM_001297.5 stop_gained

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.136

Variant links:

Genes affected

CNGB1 (HGNC:2151): (cyclic nucleotide gated channel subunit beta 1) In humans, the rod photoreceptor cGMP-gated cation channel helps regulate ion flow into the rod photoreceptor outer segment in response to light-induced alteration of the levels of intracellular cGMP. This channel consists of two subunits, alpha and beta, with the protein encoded by this gene representing the beta subunit. Defects in this gene are a cause of cause of retinitis pigmentosa type 45. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

CNGB1 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 16-57959985-G-A is Pathogenic according to our data. Variant chr16-57959985-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 437977.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-57959985-G-A is described in Lovd as [Likely_pathogenic]. Variant chr16-57959985-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CNGB1	NM_001297.5 linkuse as main transcript	c.664C>T	p.Gln222Ter	stop_gained	10/33	ENST00000251102.13	NP_001288.3
CNGB1	NM_001286130.2 linkuse as main transcript	c.646C>T	p.Gln216Ter	stop_gained	10/33		NP_001273059.1
CNGB1	NM_001135639.2 linkuse as main transcript	c.664C>T	p.Gln222Ter	stop_gained	10/13		NP_001129111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB1	ENST00000251102.13 linkuse as main transcript	c.664C>T	p.Gln222Ter	stop_gained	10/33	1	NM_001297.5	ENSP00000251102	P4	Q14028-1
CNGB1	ENST00000564448.5 linkuse as main transcript	c.646C>T	p.Gln216Ter	stop_gained	10/33	1		ENSP00000454633	A2	Q14028-4
CNGB1	ENST00000311183.8 linkuse as main transcript	c.664C>T	p.Gln222Ter	stop_gained	10/13	1		ENSP00000311670		Q14028-3
CNGB1	ENST00000562761.1 linkuse as main transcript			downstream_gene_variant		3		ENSP00000455708

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000476

AC:

AN:

210288

Hom.:

AF XY:

0.00

AC XY:

AN XY:

113570

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1438284

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712726

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Retinitis pigmentosa

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

NIHR Bioresource Rare Diseases, University of Cambridge

Jan 01, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Benign

-0.093

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.011

MutationTaster

Benign

1.0

A;A;A

Vest4

0.79

GERP RS

-0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over