16-57917490-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001297.5(CNGB1):c.1958-14A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,612,868 control chromosomes in the GnomAD database, including 58,880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7595 hom., cov: 31)

Exomes 𝑓: 0.26 ( 51285 hom. )

Consequence

CNGB1
NM_001297.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.25

Publications

6 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 (BayesDel_noAF=-0.84).

BP6

Variant 16-57917490-T-G is Benign according to our data. Variant chr16-57917490-T-G is described in ClinVar as Benign. ClinVar VariationId is 257960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB1	NM_001297.5 link	c.1958-14A>C		intron_variant	Intron 20 of 32	ENST00000251102.13	NP_001288.3	Q14028-1
CNGB1	NM_001286130.2 link	c.1940-14A>C		intron_variant	Intron 20 of 32		NP_001273059.1	Q14028-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB1	ENST00000251102.13 link	c.1958-14A>C		intron_variant	Intron 20 of 32	1	NM_001297.5	ENSP00000251102.8		Q14028-1
CNGB1	ENST00000564448.5 link	c.1940-14A>C		intron_variant	Intron 20 of 32	1		ENSP00000454633.1		Q14028-4

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46141

AN:

151748

Hom.:

7580

Cov.:

show subpopulations

Gnomad AFR

AF:

0.435

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.278

GnomAD2 exomes

AF:

0.271

AC:

67551

AN:

248924

AF XY:

0.274

show subpopulations

Gnomad AFR exome

AF:

0.435

Gnomad AMR exome

AF:

0.244

Gnomad ASJ exome

AF:

0.287

Gnomad EAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.254

Gnomad OTH exome

AF:

0.282

GnomAD4 exome

AF:

0.261

AC:

380651

AN:

1461000

Hom.:

51285

Cov.:

AF XY:

0.263

AC XY:

190952

AN XY:

726866

show subpopulations

African (AFR)

AF:

0.440

AC:

14732

AN:

33460

American (AMR)

AF:

0.244

AC:

10925

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

7468

AN:

26136

East Asian (EAS)

AF:

0.179

AC:

7106

AN:

39692

South Asian (SAS)

AF:

0.332

AC:

28623

AN:

86214

European-Finnish (FIN)

AF:

0.267

AC:

14241

AN:

53412

Middle Eastern (MID)

AF:

0.392

AC:

2140

AN:

5460

European-Non Finnish (NFE)

AF:

0.251

AC:

278797

AN:

1111568

Other (OTH)

AF:

0.275

AC:

16619

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

14857

29714

44571

59428

74285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9526

19052

28578

38104

47630

<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:

0.304

AC:

46199

AN:

151868

Hom.:

7595

Cov.:

AF XY:

0.304

AC XY:

22562

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.435

AC:

17984

AN:

41374

American (AMR)

AF:

0.245

AC:

3738

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

970

AN:

3468

East Asian (EAS)

AF:

0.172

AC:

888

AN:

5164

South Asian (SAS)

AF:

0.321

AC:

1545

AN:

4810

European-Finnish (FIN)

AF:

0.269

AC:

2840

AN:

10550

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.254

AC:

17269

AN:

67934

Other (OTH)

AF:

0.281

AC:

592

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1533

3066

4599

6132

7665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

462

924

1386

1848

2310

<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:

0.293

Hom.:

2676

Bravo

AF:

0.306

Asia WGS

AF:

0.283

AC:

988

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

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 14, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 03, 2019

GeneDx

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

- -

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

-0.84

CADD

Benign

0.094

(source)

DANN

Benign

0.36

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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