16-57903952-G-C

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>G(p.Ala888Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 1,613,534 control chromosomes in the GnomAD database, including 470,130 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 0.68 ( 37045 hom., cov: 33)

Exomes 𝑓: 0.77 ( 433085 hom. )

Consequence

CNGB1
NM_001297.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

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-C is Benign according to our data. Variant chr16-57903952-G-C is described in ClinVar as Benign. ClinVar VariationId is 166894.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 (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGB1	NM_001297.5	MANE Select	c.2664C>G	p.Ala888Ala	synonymous	Exon 27 of 33	NP_001288.3
	CNGB1	NM_001286130.2		c.2646C>G	p.Ala882Ala	synonymous	Exon 27 of 33	NP_001273059.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CNGB1	ENST00000251102.13	TSL:1 MANE Select	c.2664C>G	p.Ala888Ala	synonymous	Exon 27 of 33	ENSP00000251102.8
CNGB1	ENST00000564448.5	TSL:1	c.2646C>G	p.Ala882Ala	synonymous	Exon 27 of 33	ENSP00000454633.1
CNGB1	ENST00000569643.1	TSL:5	n.321C>G		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes

AF:

0.682

AC:

103729

AN:

152092

Hom.:

37041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.444

Gnomad AMI

AF:

0.891

Gnomad AMR

AF:

0.743

Gnomad ASJ

AF:

0.691

Gnomad EAS

AF:

0.917

Gnomad SAS

AF:

0.830

Gnomad FIN

AF:

0.809

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.761

Gnomad OTH

AF:

0.711

GnomAD2 exomes

AF:

0.765

AC:

190370

AN:

248746

AF XY:

0.773

show subpopulations

Gnomad AFR exome

AF:

0.438

Gnomad AMR exome

AF:

0.762

Gnomad ASJ exome

AF:

0.700

Gnomad EAS exome

AF:

0.918

Gnomad FIN exome

AF:

0.817

Gnomad NFE exome

AF:

0.766

Gnomad OTH exome

AF:

0.760

GnomAD4 exome

AF:

0.767

AC:

1120710

AN:

1461324

Hom.:

433085

Cov.:

AF XY:

0.770

AC XY:

559583

AN XY:

726942

show subpopulations

African (AFR)

AF:

0.437

AC:

14620

AN:

33470

American (AMR)

AF:

0.761

AC:

34004

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

18101

AN:

26130

East Asian (EAS)

AF:

0.936

AC:

37141

AN:

39698

South Asian (SAS)

AF:

0.830

AC:

71555

AN:

86238

European-Finnish (FIN)

AF:

0.817

AC:

43622

AN:

53394

Middle Eastern (MID)

AF:

0.688

AC:

3912

AN:

5688

European-Non Finnish (NFE)

AF:

0.767

AC:

852456

AN:

1111658

Other (OTH)

AF:

0.751

AC:

45299

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

13519

27038

40556

54075

67594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20434

40868

61302

81736

102170

<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:

0.682

AC:

103771

AN:

152210

Hom.:

37045

Cov.:

AF XY:

0.689

AC XY:

51248

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.444

AC:

18439

AN:

41522

American (AMR)

AF:

0.744

AC:

11372

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.691

AC:

2395

AN:

3468

East Asian (EAS)

AF:

0.918

AC:

4740

AN:

5166

South Asian (SAS)

AF:

0.829

AC:

3998

AN:

4824

European-Finnish (FIN)

AF:

0.809

AC:

8571

AN:

10600

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.761

AC:

51750

AN:

68016

Other (OTH)

AF:

0.712

AC:

1506

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1594

3188

4783

6377

7971

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.714

Hom.:

3683

EpiCase

AF:

0.755

EpiControl

AF:

0.762

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Jan 17, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Retinitis pigmentosa 45

Benign:2

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.035

(source)

DANN

Benign

0.33

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over