rs13265557

Variant names:

Variant summary

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

The NM_019098.5(CNGB3):c.919A>G(p.Ile307Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 1,590,968 control chromosomes in the GnomAD database, including 3,760 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 310 hom., cov: 32)

Exomes 𝑓: 0.065 ( 3450 hom. )

Consequence

CNGB3
NM_019098.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.332

Publications

23 publications found

Variant links:

Genes affected

CNGB3 (HGNC:2153): (cyclic nucleotide gated channel subunit beta 3) This gene encodes the beta subunit of a cyclic nucleotide-gated ion channel. The encoded beta subunit appears to play a role in modulation of channel function in cone photoreceptors. This heterotetrameric channel is necessary for sensory transduction, and mutations in this gene have been associated with achromatopsia 3, progressive cone dystrophy, and juvenile macular degeneration, also known as Stargardt Disease. [provided by RefSeq, Feb 2010]

CNGB3 Gene-Disease associations (from GenCC):

achromatopsia 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
CNGB3-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cone dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
achromatopsia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
severe early-childhood-onset retinal dystrophy
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CNGB3 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=0.0023343265).

BP6

Variant 8-86647872-T-C is Benign according to our data. Variant chr8-86647872-T-C is described in ClinVar as Benign. ClinVar VariationId is 261092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB3	NM_019098.5 link	c.919A>G	p.Ile307Val	missense_variant	Exon 8 of 18	ENST00000320005.6	NP_061971.3	Q9NQW8-1
CNGB3	XM_011517138.3 link	c.505A>G	p.Ile169Val	missense_variant	Exon 6 of 16		XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CNGB3	ENST00000320005.6 link	c.919A>G	p.Ile307Val	missense_variant	Exon 8 of 18	1	NM_019098.5	ENSP00000316605.5	Q9NQW8-1
CNGB3	ENST00000681546.1 link	n.739A>G		non_coding_transcript_exon_variant	Exon 3 of 13
CNGB3	ENST00000681746.1 link	n.919A>G		non_coding_transcript_exon_variant	Exon 8 of 19			ENSP00000505959.1	A0A5J6DSN8

Frequencies

GnomAD3 genomes

AF:

0.0601

AC:

9085

AN:

151164

Hom.:

308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0477

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0545

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.0645

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.0900

Gnomad MID

AF:

0.0446

Gnomad NFE

AF:

0.0621

Gnomad OTH

AF:

0.0592

GnomAD2 exomes

AF:

0.0692

AC:

17292

AN:

249968

AF XY:

0.0710

show subpopulations

Gnomad AFR exome

AF:

0.0470

Gnomad AMR exome

AF:

0.0682

Gnomad ASJ exome

AF:

0.0357

Gnomad EAS exome

AF:

0.0534

Gnomad FIN exome

AF:

0.0862

Gnomad NFE exome

AF:

0.0641

Gnomad OTH exome

AF:

0.0669

GnomAD4 exome

AF:

0.0654

AC:

94092

AN:

1439684

Hom.:

3450

Cov.:

AF XY:

0.0666

AC XY:

47794

AN XY:

717442

show subpopulations

African (AFR)

AF:

0.0460

AC:

1517

AN:

32986

American (AMR)

AF:

0.0675

AC:

3009

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.0345

AC:

894

AN:

25908

East Asian (EAS)

AF:

0.0793

AC:

3129

AN:

39438

South Asian (SAS)

AF:

0.107

AC:

9141

AN:

85640

European-Finnish (FIN)

AF:

0.0834

AC:

4453

AN:

53372

Middle Eastern (MID)

AF:

0.0411

AC:

234

AN:

5696

European-Non Finnish (NFE)

AF:

0.0620

AC:

67732

AN:

1092562

Other (OTH)

AF:

0.0669

AC:

3983

AN:

59530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

3680

7359

11039

14718

18398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2534

5068

7602

10136

12670

<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:

0.0602

AC:

9103

AN:

151284

Hom.:

310

Cov.:

AF XY:

0.0619

AC XY:

4579

AN XY:

73992

show subpopulations

African (AFR)

AF:

0.0479

AC:

1985

AN:

41454

American (AMR)

AF:

0.0546

AC:

828

AN:

15166

Ashkenazi Jewish (ASJ)

AF:

0.0337

AC:

116

AN:

3446

East Asian (EAS)

AF:

0.0651

AC:

337

AN:

5178

South Asian (SAS)

AF:

0.110

AC:

529

AN:

4826

European-Finnish (FIN)

AF:

0.0900

AC:

956

AN:

10620

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0621

AC:

4177

AN:

67290

Other (OTH)

AF:

0.0610

AC:

128

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

428

856

1283

1711

2139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0608

Hom.:

615

Bravo

AF:

0.0552

TwinsUK

AF:

0.0588

AC:

218

ALSPAC

AF:

0.0667

AC:

257

ESP6500AA

AF:

0.0520

AC:

229

ESP6500EA

AF:

0.0599

AC:

515

ExAC

AF:

0.0709

AC:

8606

Asia WGS

AF:

0.126

AC:

436

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 19, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Achromatopsia 3

Benign:2

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

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

- -

Achromatopsia

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Severe early-childhood-onset retinal dystrophy

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.023

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.39

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0023

MetaSVM

Benign

-0.58

MutationAssessor

Benign

-0.15

PhyloP100

-0.33

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.67

REVEL

Benign

0.26

Sift

Benign

0.37

Sift4G

Benign

0.30

Polyphen

0.0010

Vest4

0.020

MPC

0.026

ClinPred

0.00080

GERP RS

-6.9

Varity_R

0.036

gMVP

0.43

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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