rs16916632

Positions:

chr8-86668054-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBA1

The NM_019098.5(CNGB3):c.608G>A(p.Arg203Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00948 in 1,613,782 control chromosomes in the GnomAD database, including 1,054 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R203?) has been classified as Pathogenic.

Frequency

Genomes: 𝑓 0.047 ( 552 hom., cov: 31)

Exomes 𝑓: 0.0056 ( 502 hom. )

Consequence

CNGB3
NM_019098.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.856

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 -18 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr8-86668053-TCG-TA is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.0015887618).

BP6

Variant 8-86668054-C-T is Benign according to our data. Variant chr8-86668054-C-T is described in ClinVar as [Benign]. Clinvar id is 261089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-86668054-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 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.608G>A	p.Arg203Gln	missense_variant	5/18	ENST00000320005.6	NP_061971.3
CNGB3	XM_011517138.3 linkuse as main transcript	c.194G>A	p.Arg65Gln	missense_variant	3/16		XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6 linkuse as main transcript	c.608G>A	p.Arg203Gln	missense_variant	5/18	1	NM_019098.5	ENSP00000316605	P1	Q9NQW8-1
CNGB3	ENST00000681746.1 linkuse as main transcript	c.608G>A	p.Arg203Gln	missense_variant, NMD_transcript_variant	5/19			ENSP00000505959

Frequencies

GnomAD3 genomes

AF:

0.0469

AC:

7121

AN:

151846

Hom.:

549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0176

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00522

Gnomad SAS

AF:

0.0104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0378

GnomAD3 exomes

AF:

0.0147

AC:

3695

AN:

251418

Hom.:

251

AF XY:

0.0115

AC XY:

1558

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.00943

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00696

Gnomad SAS exome

AF:

0.0114

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.00558

AC:

8159

AN:

1461820

Hom.:

502

Cov.:

AF XY:

0.00513

AC XY:

3730

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.0106

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00383

Gnomad4 SAS exome

AF:

0.0112

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000311

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.0470

AC:

7137

AN:

151962

Hom.:

552

Cov.:

AF XY:

0.0443

AC XY:

3289

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.0176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00523

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.0374

Alfa

AF:

0.00959

Hom.:

151

Bravo

AF:

0.0543

ESP6500AA

AF:

0.154

AC:

679

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0174

AC:

2113

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Achromatopsia

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Dec 02, 2019

- -

Severe early-childhood-onset retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.98

DANN

Benign

0.83

DEOGEN2

Benign

0.072

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.73

REVEL

Benign

0.25

Sift

Benign

0.25

Sift4G

Benign

0.63

Polyphen

0.0010

Vest4

0.040

MPC

0.029

ClinPred

0.0031

GERP RS

-6.8

Varity_R

0.037

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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