chr16-57901566-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

CNGB1-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa 45
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CNGB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 235409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 57 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB1	NM_001297.5 link	c.2854G>A	p.Val952Met	missense_variant	Exon 28 of 33	ENST00000251102.13	NP_001288.3	Q14028-1
CNGB1	NM_001286130.2 link	c.2836G>A	p.Val946Met	missense_variant	Exon 28 of 33		NP_001273059.1	Q14028-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CNGB1	ENST00000251102.13 link	c.2854G>A	p.Val952Met	missense_variant	Exon 28 of 33	1	NM_001297.5	ENSP00000251102.8	Q14028-1
CNGB1	ENST00000564448.5 link	c.2836G>A	p.Val946Met	missense_variant	Exon 28 of 33	1		ENSP00000454633.1	Q14028-4
CNGB1	ENST00000569643.1 link	n.511G>A		non_coding_transcript_exon_variant	Exon 4 of 6	5
CNGB1	ENST00000565942.1 link	c.-194G>A		upstream_gene_variant		5		ENSP00000455964.1	H3BQW3

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

GnomAD2 exomes

AF:

0.0108

AC:

2707

AN:

249550

AF XY:

0.00962

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 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

African (AFR)

AF:

0.0485

AC:

1624

AN:

33478

American (AMR)

AF:

0.00579

AC:

259

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0170

AC:

444

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00184

AC:

159

AN:

86258

European-Finnish (FIN)

AF:

0.00891

AC:

476

AN:

53416

Middle Eastern (MID)

AF:

0.0314

AC:

181

AN:

5762

European-Non Finnish (NFE)

AF:

0.0110

AC:

12219

AN:

1112000

Other (OTH)

AF:

0.0126

AC:

762

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

961

1922

2884

3845

4806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

496

992

1488

1984

2480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0204

AC:

3105

AN:

152252

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

1440

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0486

AC:

2021

AN:

41546

American (AMR)

AF:

0.00869

AC:

133

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00104

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00660

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0111

AC:

756

AN:

68018

Other (OTH)

AF:

0.0246

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

158

316

473

631

789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0143

Hom.:

104

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 11, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa 45

Benign:1

Nov 09, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinal dystrophy

Benign:1

Jan 01, 2013

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

(source)

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;.

PhyloP100

7.9

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

PromoterAI

0.0051

Neutral

(source)

Varity_R

0.21

gMVP

0.44

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over