rs79889567

Positions:

chr16-57901566-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001297.5(CNGB1):c.2854G>A(p.Val952Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,614,112 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 57 hom., cov: 32)

Exomes 𝑓: 0.011 ( 118 hom. )

Consequence

CNGB1
NM_001297.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 7.88

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:

CNGB1 (HGNC:):

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 (MetaRNN=0.011026382).

BP6

Variant 16-57901566-C-T is Benign according to our data. Variant chr16-57901566-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 235409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-57901566-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0204 (3105/152252) while in subpopulation AFR AF= 0.0486 (2021/41546). AF 95% confidence interval is 0.0469. There are 57 homozygotes in gnomad4. There are 1440 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB1	NM_001297.5 linkuse as main transcript	c.2854G>A	p.Val952Met	missense_variant	28/33	ENST00000251102.13	NP_001288.3	Q14028-1
CNGB1	NM_001286130.2 linkuse as main transcript	c.2836G>A	p.Val946Met	missense_variant	28/33		NP_001273059.1	Q14028-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CNGB1	ENST00000251102.13 linkuse as main transcript	c.2854G>A	p.Val952Met	missense_variant	28/33	1	NM_001297.5	ENSP00000251102.8	Q14028-1
CNGB1	ENST00000564448.5 linkuse as main transcript	c.2836G>A	p.Val946Met	missense_variant	28/33	1		ENSP00000454633.1	Q14028-4
CNGB1	ENST00000569643.1 linkuse as main transcript	n.511G>A		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.0204

AC:

3101

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00871

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00660

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.0248

GnomAD3 exomes

AF:

0.0108

AC:

2707

AN:

249550

Hom.:

AF XY:

0.00962

AC XY:

1303

AN XY:

135384

show subpopulations

Gnomad AFR exome

AF:

0.0504

Gnomad AMR exome

AF:

0.00504

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00150

Gnomad FIN exome

AF:

0.00923

Gnomad NFE exome

AF:

0.0112

Gnomad OTH exome

AF:

0.0117

GnomAD4 exome

AF:

0.0110

AC:

16126

AN:

1461860

Hom.:

118

Cov.:

AF XY:

0.0106

AC XY:

7729

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0485

Gnomad4 AMR exome

AF:

0.00579

Gnomad4 ASJ exome

AF:

0.0170

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00184

Gnomad4 FIN exome

AF:

0.00891

Gnomad4 NFE exome

AF:

0.0110

Gnomad4 OTH exome

AF:

0.0126

GnomAD4 genome

AF:

0.0204

AC:

3105

AN:

152252

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

1440

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0486

Gnomad4 AMR

AF:

0.00869

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00660

Gnomad4 NFE

AF:

0.0111

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0131

Hom.:

Bravo

AF:

0.0220

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.0479

AC:

199

ESP6500EA

AF:

0.00853

AC:

ExAC

AF:

0.0114

AC:

1384

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.0110

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 11, 2016	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Retinitis pigmentosa 45

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 09, 2023

- -

Retinal dystrophy

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D

MetaRNN

Benign

0.011

T;T

MetaSVM

Uncertain

-0.075

MutationAssessor

Benign

1.9

M;.

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-2.3

N;N

REVEL

Pathogenic

0.77

Sift

Uncertain

0.025

D;D

Sift4G

Uncertain

0.036

D;D

Polyphen

0.99

D;.

Vest4

0.29

MPC

0.28

ClinPred

0.020

GERP RS

4.6

Varity_R

0.21

gMVP

0.44

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