8-86575970-T-C

Position:

chr8-86575970-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019098.5(CNGB3):c.2264A>G(p.Glu755Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 1,613,852 control chromosomes in the GnomAD database, including 6,663 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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 ( 6088 hom. )

Consequence

CNGB3
NM_019098.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.315

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027657747).

BP6

Variant 8-86575970-T-C is Benign according to our data. Variant chr8-86575970-T-C is described in ClinVar as [Benign]. Clinvar id is 166899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-86575970-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB3	NM_019098.5 linkuse as main transcript	c.2264A>G	p.Glu755Gly	missense_variant	18/18	ENST00000320005.6	NP_061971.3
CNGB3	XM_011517138.3 linkuse as main transcript	c.1850A>G	p.Glu617Gly	missense_variant	16/16		XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6 linkuse as main transcript	c.2264A>G	p.Glu755Gly	missense_variant	18/18	1	NM_019098.5	ENSP00000316605	P1	Q9NQW8-1
CNGB3	ENST00000517327.5 linkuse as main transcript	c.276+2719A>G		intron_variant		3		ENSP00000428329
CNGB3	ENST00000681546.1 linkuse as main transcript	n.2084A>G		non_coding_transcript_exon_variant	13/13
CNGB3	ENST00000681746.1 linkuse as main transcript	c.*675A>G		3_prime_UTR_variant, NMD_transcript_variant	19/19			ENSP00000505959

Frequencies

GnomAD3 genomes

AF:

0.0822

AC:

12513

AN:

152144

Hom.:

576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0702

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.0616

Gnomad ASJ

AF:

0.0623

Gnomad EAS

AF:

0.0997

Gnomad SAS

AF:

0.0744

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0902

Gnomad OTH

AF:

0.0718

GnomAD3 exomes

AF:

0.0867

AC:

21800

AN:

251370

Hom.:

983

AF XY:

0.0869

AC XY:

11802

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.0738

Gnomad AMR exome

AF:

0.0780

Gnomad ASJ exome

AF:

0.0600

Gnomad EAS exome

AF:

0.0878

Gnomad SAS exome

AF:

0.0813

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.0909

Gnomad OTH exome

AF:

0.0860

GnomAD4 exome

AF:

0.0895

AC:

130776

AN:

1461588

Hom.:

6088

Cov.:

AF XY:

0.0889

AC XY:

64611

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.0687

Gnomad4 AMR exome

AF:

0.0780

Gnomad4 ASJ exome

AF:

0.0595

Gnomad4 EAS exome

AF:

0.114

Gnomad4 SAS exome

AF:

0.0796

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.0903

Gnomad4 OTH exome

AF:

0.0902

GnomAD4 genome

AF:

0.0823

AC:

12526

AN:

152264

Hom.:

575

Cov.:

AF XY:

0.0830

AC XY:

6177

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0702

Gnomad4 AMR

AF:

0.0616

Gnomad4 ASJ

AF:

0.0623

Gnomad4 EAS

AF:

0.0999

Gnomad4 SAS

AF:

0.0755

Gnomad4 FIN

AF:

0.112

Gnomad4 NFE

AF:

0.0902

Gnomad4 OTH

AF:

0.0724

Alfa

AF:

0.0859

Hom.:

1446

Bravo

AF:

0.0790

TwinsUK

AF:

0.0814

AC:

302

ALSPAC

AF:

0.0921

AC:

355

ESP6500AA

AF:

0.0704

AC:

310

ESP6500EA

AF:

0.0864

AC:

743

ExAC

AF:

0.0872

AC:

10593

Asia WGS

AF:

0.118

AC:

409

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 25, 2014	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 19, 2016	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Achromatopsia

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Severe early-childhood-onset retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.36

CADD

Benign

8.8

DANN

Benign

0.96

DEOGEN2

Benign

0.12

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.6

REVEL

Benign

0.22

Sift

Benign

0.032

Sift4G

Benign

0.23

Polyphen

0.12

Vest4

0.016

MPC

0.033

ClinPred

0.0054

GERP RS

3.0

Varity_R

0.072

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over