rs3735970

Variant names:

Variant summary

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

The NM_019098.5(CNGB3):c.2214A>G(p.Glu738Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 1,610,886 control chromosomes in the GnomAD database, including 6,655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 575 hom., cov: 32)

Exomes 𝑓: 0.089 ( 6080 hom. )

Consequence

CNGB3
NM_019098.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.922

Publications

15 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 8-86576020-T-C is Benign according to our data. Variant chr8-86576020-T-C is described in ClinVar as [Benign]. Clinvar id is 166903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.922 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB3	NM_019098.5 link	c.2214A>G	p.Glu738Glu	synonymous_variant	Exon 18 of 18	ENST00000320005.6	NP_061971.3	Q9NQW8-1
CNGB3	XM_011517138.3 link	c.1800A>G	p.Glu600Glu	synonymous_variant	Exon 16 of 16		XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6 link	c.2214A>G	p.Glu738Glu	synonymous_variant	Exon 18 of 18	1	NM_019098.5	ENSP00000316605.5		Q9NQW8-1

Frequencies

GnomAD3 genomes

AF:

0.0822

AC:

12503

AN:

152062

Hom.:

576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0701

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.0616

Gnomad ASJ

AF:

0.0623

Gnomad EAS

AF:

0.0995

Gnomad SAS

AF:

0.0742

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0902

Gnomad OTH

AF:

0.0722

GnomAD2 exomes

AF:

0.0870

AC:

21748

AN:

250102

AF XY:

0.0871

show subpopulations

Gnomad AFR exome

AF:

0.0740

Gnomad AMR exome

AF:

0.0781

Gnomad ASJ exome

AF:

0.0601

Gnomad EAS exome

AF:

0.0881

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.0912

Gnomad OTH exome

AF:

0.0862

GnomAD4 exome

AF:

0.0892

AC:

130163

AN:

1458706

Hom.:

6080

Cov.:

AF XY:

0.0887

AC XY:

64337

AN XY:

725714

show subpopulations

African (AFR)

AF:

0.0688

AC:

2296

AN:

33392

American (AMR)

AF:

0.0779

AC:

3477

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.0594

AC:

1553

AN:

26124

East Asian (EAS)

AF:

0.113

AC:

4501

AN:

39678

South Asian (SAS)

AF:

0.0796

AC:

6816

AN:

85674

European-Finnish (FIN)

AF:

0.109

AC:

5830

AN:

53378

Middle Eastern (MID)

AF:

0.0593

AC:

340

AN:

5738

European-Non Finnish (NFE)

AF:

0.0900

AC:

99924

AN:

1109830

Other (OTH)

AF:

0.0900

AC:

5426

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

5734

11467

17201

22934

28668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3652

7304

10956

14608

18260

<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:

0.0822

AC:

12516

AN:

152180

Hom.:

575

Cov.:

AF XY:

0.0830

AC XY:

6172

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0701

AC:

2910

AN:

41520

American (AMR)

AF:

0.0616

AC:

941

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0623

AC:

216

AN:

3468

East Asian (EAS)

AF:

0.0998

AC:

516

AN:

5172

South Asian (SAS)

AF:

0.0753

AC:

363

AN:

4818

European-Finnish (FIN)

AF:

0.112

AC:

1192

AN:

10604

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0902

AC:

6131

AN:

68000

Other (OTH)

AF:

0.0728

AC:

154

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

589

1179

1768

2358

2947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<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:

0.0874

Hom.:

307

Bravo

AF:

0.0790

Asia WGS

AF:

0.117

AC:

408

AN:

3478

EpiCase

AF:

0.0829

EpiControl

AF:

0.0806

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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. -

Apr 25, 2014

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

- -

not provided

Benign:2

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

- -

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 12, 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. -

Achromatopsia 3

Benign:1

Jan 12, 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

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.4

(source)

DANN

Benign

0.63

PhyloP100

-0.92

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