rs437920

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001297.5(CNGB1):c.2635-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 1,611,120 control chromosomes in the GnomAD database, including 560,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 46809 hom., cov: 32)

Exomes 𝑓: 0.84 ( 514088 hom. )

Consequence

CNGB1
NM_001297.5 intron

Scores

Splicing: ADA: 0.00001391

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.181

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-57903991-G-A is Benign according to our data. Variant chr16-57903991-G-A is described in ClinVar as [Benign]. Clinvar id is 166895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-57903991-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB1	NM_001297.5 link	c.2635-10C>T		intron_variant		ENST00000251102.13	NP_001288.3	Q14028-1
CNGB1	NM_001286130.2 link	c.2617-10C>T		intron_variant			NP_001273059.1	Q14028-4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CNGB1	ENST00000251102.13 link	c.2635-10C>T	intron_variant	1	NM_001297.5	ENSP00000251102.8	Q14028-1
CNGB1	ENST00000564448.5 link	c.2617-10C>T	intron_variant	1		ENSP00000454633.1	Q14028-4
CNGB1	ENST00000569643.1 link	n.292-10C>T	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.779

AC:

118400

AN:

151902

Hom.:

46783

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

0.915

Gnomad AMR

AF:

0.778

Gnomad ASJ

AF:

0.782

Gnomad EAS

AF:

0.651

Gnomad SAS

AF:

0.876

Gnomad FIN

AF:

0.829

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.848

Gnomad OTH

AF:

0.802

GnomAD3 exomes

AF:

0.812

AC:

200545

AN:

246984

Hom.:

82116

AF XY:

0.822

AC XY:

110075

AN XY:

133974

show subpopulations

Gnomad AFR exome

AF:

0.661

Gnomad AMR exome

AF:

0.763

Gnomad ASJ exome

AF:

0.787

Gnomad EAS exome

AF:

0.657

Gnomad SAS exome

AF:

0.874

Gnomad FIN exome

AF:

0.841

Gnomad NFE exome

AF:

0.852

Gnomad OTH exome

AF:

0.813

GnomAD4 exome

AF:

0.838

AC:

1222308

AN:

1459100

Hom.:

514088

Cov.:

AF XY:

0.840

AC XY:

609496

AN XY:

725852

show subpopulations

Gnomad4 AFR exome

AF:

0.655

Gnomad4 AMR exome

AF:

0.765

Gnomad4 ASJ exome

AF:

0.783

Gnomad4 EAS exome

AF:

0.644

Gnomad4 SAS exome

AF:

0.874

Gnomad4 FIN exome

AF:

0.842

Gnomad4 NFE exome

AF:

0.853

Gnomad4 OTH exome

AF:

0.817

GnomAD4 genome

AF:

0.779

AC:

118477

AN:

152020

Hom.:

46809

Cov.:

AF XY:

0.779

AC XY:

57851

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.655

Gnomad4 AMR

AF:

0.778

Gnomad4 ASJ

AF:

0.782

Gnomad4 EAS

AF:

0.651

Gnomad4 SAS

AF:

0.878

Gnomad4 FIN

AF:

0.829

Gnomad4 NFE

AF:

0.848

Gnomad4 OTH

AF:

0.802

Alfa

AF:

0.806

Hom.:

19244

Bravo

AF:

0.768

Asia WGS

AF:

0.755

AC:

2626

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 27, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Retinitis pigmentosa 45

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.88

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0040

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