Variant 8-86574165-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000517327.5(CNGB3):c.276+4524C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,954 control chromosomes in the GnomAD database, including 28,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 28316 hom., cov: 31)

Exomes 𝑓: 1.0 ( 1 hom. )

Consequence

CNGB3
ENST00000517327.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.647

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 8-86574165-G-T is Benign according to our data. Variant chr8-86574165-G-T is described in ClinVar as [Benign]. Clinvar id is 363844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB3	NM_019098.5 link	c.*1639C>A		downstream_gene_variant		ENST00000320005.6	NP_061971.3	Q9NQW8-1
CNGB3	XM_011517138.3 link	c.*1639C>A		downstream_gene_variant			XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6 link	c.*1639C>A		downstream_gene_variant		1	NM_019098.5	ENSP00000316605.5		Q9NQW8-1

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89720

AN:

151834

Hom.:

28308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.357

Gnomad AMI

AF:

0.712

Gnomad AMR

AF:

0.691

Gnomad ASJ

AF:

0.680

Gnomad EAS

AF:

0.501

Gnomad SAS

AF:

0.636

Gnomad FIN

AF:

0.691

Gnomad MID

AF:

0.671

Gnomad NFE

AF:

0.693

Gnomad OTH

AF:

0.580

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

Gnomad4 NFE exome

AF:

1.00

GnomAD4 genome

AF:

0.591

AC:

89744

AN:

151952

Hom.:

28316

Cov.:

AF XY:

0.591

AC XY:

43874

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.356

Gnomad4 AMR

AF:

0.691

Gnomad4 ASJ

AF:

0.680

Gnomad4 EAS

AF:

0.501

Gnomad4 SAS

AF:

0.637

Gnomad4 FIN

AF:

0.691

Gnomad4 NFE

AF:

0.693

Gnomad4 OTH

AF:

0.572

Alfa

AF:

0.665

Hom.:

25195

Bravo

AF:

0.579

Asia WGS

AF:

0.503

AC:

1748

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

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 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.27

DANN

Benign

0.47

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