16-57903952-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001297.5(CNGB1):c.2664C>A(p.Ala888Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,613,682 control chromosomes in the GnomAD database, including 11,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A888A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.15 ( 1967 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9437 hom. )

Consequence

CNGB1
NM_001297.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -8.35

Publications

19 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 16-57903952-G-T is Benign according to our data. Variant chr16-57903952-G-T is described in ClinVar as Benign. ClinVar VariationId is 93700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB1	NM_001297.5 link	c.2664C>A	p.Ala888Ala	synonymous_variant	Exon 27 of 33	ENST00000251102.13	NP_001288.3
CNGB1	NM_001286130.2 link	c.2646C>A	p.Ala882Ala	synonymous_variant	Exon 27 of 33		NP_001273059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CNGB1	ENST00000251102.13 link	c.2664C>A	p.Ala888Ala	synonymous_variant	Exon 27 of 33	1	NM_001297.5	ENSP00000251102.8
CNGB1	ENST00000564448.5 link	c.2646C>A	p.Ala882Ala	synonymous_variant	Exon 27 of 33	1		ENSP00000454633.1
CNGB1	ENST00000569643.1 link	n.321C>A		non_coding_transcript_exon_variant	Exon 3 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22158

AN:

152064

Hom.:

1964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.0940

Gnomad EAS

AF:

0.0825

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.0484

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.133

GnomAD2 exomes

AF:

0.117

AC:

29178

AN:

248746

AF XY:

0.113

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.0909

Gnomad EAS exome

AF:

0.0818

Gnomad FIN exome

AF:

0.0523

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.108

AC:

158551

AN:

1461500

Hom.:

9437

Cov.:

AF XY:

0.108

AC XY:

78517

AN XY:

727052

show subpopulations

African (AFR)

AF:

0.261

AC:

8741

AN:

33470

American (AMR)

AF:

0.160

AC:

7156

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0937

AC:

2448

AN:

26130

East Asian (EAS)

AF:

0.0642

AC:

2549

AN:

39698

South Asian (SAS)

AF:

0.118

AC:

10176

AN:

86240

European-Finnish (FIN)

AF:

0.0536

AC:

2861

AN:

53398

Middle Eastern (MID)

AF:

0.118

AC:

673

AN:

5688

European-Non Finnish (NFE)

AF:

0.105

AC:

117240

AN:

1111802

Other (OTH)

AF:

0.111

AC:

6707

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

7737

15473

23210

30946

38683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4398

8796

13194

17592

21990

<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:

0.146

AC:

22200

AN:

152182

Hom.:

1967

Cov.:

AF XY:

0.142

AC XY:

10591

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.254

AC:

10547

AN:

41514

American (AMR)

AF:

0.148

AC:

2265

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0940

AC:

326

AN:

3468

East Asian (EAS)

AF:

0.0819

AC:

423

AN:

5166

South Asian (SAS)

AF:

0.125

AC:

601

AN:

4820

European-Finnish (FIN)

AF:

0.0484

AC:

513

AN:

10602

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.105

AC:

7171

AN:

68012

Other (OTH)

AF:

0.134

AC:

283

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

900

1801

2701

3602

4502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<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:

0.105

Hom.:

3683

EpiCase

AF:

0.100

EpiControl

AF:

0.101

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

Oct 23, 2013

Eurofins Ntd Llc (ga)

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:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Retinitis pigmentosa

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

-0.88

CADD

Benign

0.030

(source)

DANN

Benign

0.31

PhyloP100

-8.4

Mutation Taster

=100/0

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