rs75858066

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_019098.5(CNGB3):c.354G>T(p.Pro118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,613,354 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P118P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0096 ( 23 hom., cov: 32)

Exomes 𝑓: 0.00096 ( 17 hom. )

Consequence

CNGB3
NM_019098.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.416

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 8-86671083-C-A is Benign according to our data. Variant chr8-86671083-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 261088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.416 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00958 (1454/151764) while in subpopulation AFR AF= 0.0331 (1368/41366). AF 95% confidence interval is 0.0316. There are 23 homozygotes in gnomad4. There are 700 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNGB3	NM_019098.5 linkuse as main transcript	c.354G>T	p.Pro118=	synonymous_variant	4/18	ENST00000320005.6
CNGB3	XM_011517138.3 linkuse as main transcript	c.-61G>T		5_prime_UTR_variant	2/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNGB3	ENST00000320005.6 linkuse as main transcript	c.354G>T	p.Pro118=	synonymous_variant	4/18	1	NM_019098.5	P1	Q9NQW8-1
CNGB3	ENST00000680314.1 linkuse as main transcript	n.115G>T		non_coding_transcript_exon_variant	2/3
CNGB3	ENST00000681746.1 linkuse as main transcript	c.354G>T	p.Pro118=	synonymous_variant, NMD_transcript_variant	4/19

Frequencies

GnomAD3 genomes

AF:

0.00959

AC:

1455

AN:

151646

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0332

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00408

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00239

AC:

600

AN:

251238

Hom.:

AF XY:

0.00180

AC XY:

245

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.0337

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000960

AC:

1403

AN:

1461590

Hom.:

Cov.:

AF XY:

0.000821

AC XY:

597

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.0357

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00958

AC:

1454

AN:

151764

Hom.:

Cov.:

AF XY:

0.00944

AC XY:

700

AN XY:

74114

show subpopulations

Gnomad4 AFR

AF:

0.0331

Gnomad4 AMR

AF:

0.00407

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.000939

Hom.:

Bravo

AF:

0.0107

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Apr 28, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Achromatopsia 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 28, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.72

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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