Variant rs3735969 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 NM_019098.5(CNGB3):c.1179-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.07 in 1,585,200 control chromosomes in the GnomAD database, including 4,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 292 hom., cov: 32)

Exomes 𝑓: 0.072 ( 3953 hom. )

Consequence

CNGB3
NM_019098.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.27

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 8-86632931-A-G is Benign according to our data. Variant chr8-86632931-A-G is described in ClinVar as [Benign]. Clinvar id is 261081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0704 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.1179-38T>C		intron_variant		ENST00000320005.6	NP_061971.3
CNGB3	XM_011517138.3 linkuse as main transcript	c.765-38T>C		intron_variant			XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6 linkuse as main transcript	c.1179-38T>C	intron_variant	1	NM_019098.5	ENSP00000316605	P1	Q9NQW8-1
CNGB3	ENST00000681746.1 linkuse as main transcript	c.1179-38T>C	intron_variant, NMD_transcript_variant			ENSP00000505959
CNGB3	ENST00000681546.1 linkuse as main transcript	n.999-38T>C	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0530

AC:

8065

AN:

152162

Hom.:

291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0483

Gnomad ASJ

AF:

0.0372

Gnomad EAS

AF:

0.0582

Gnomad SAS

AF:

0.0766

Gnomad FIN

AF:

0.0954

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0694

Gnomad OTH

AF:

0.0536

GnomAD3 exomes

AF:

0.0661

AC:

16394

AN:

248102

Hom.:

623

AF XY:

0.0674

AC XY:

9046

AN XY:

134294

show subpopulations

Gnomad AFR exome

AF:

0.0133

Gnomad AMR exome

AF:

0.0663

Gnomad ASJ exome

AF:

0.0402

Gnomad EAS exome

AF:

0.0492

Gnomad SAS exome

AF:

0.0762

Gnomad FIN exome

AF:

0.0922

Gnomad NFE exome

AF:

0.0707

Gnomad OTH exome

AF:

0.0676

GnomAD4 exome

AF:

0.0718

AC:

102840

AN:

1432920

Hom.:

3953

Cov.:

AF XY:

0.0716

AC XY:

51172

AN XY:

714548

show subpopulations

Gnomad4 AFR exome

AF:

0.0135

Gnomad4 AMR exome

AF:

0.0653

Gnomad4 ASJ exome

AF:

0.0397

Gnomad4 EAS exome

AF:

0.0764

Gnomad4 SAS exome

AF:

0.0751

Gnomad4 FIN exome

AF:

0.0901

Gnomad4 NFE exome

AF:

0.0736

Gnomad4 OTH exome

AF:

0.0673

GnomAD4 genome

AF:

0.0530

AC:

8070

AN:

152280

Hom.:

292

Cov.:

AF XY:

0.0539

AC XY:

4011

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0155

Gnomad4 AMR

AF:

0.0484

Gnomad4 ASJ

AF:

0.0372

Gnomad4 EAS

AF:

0.0585

Gnomad4 SAS

AF:

0.0768

Gnomad4 FIN

AF:

0.0954

Gnomad4 NFE

AF:

0.0694

Gnomad4 OTH

AF:

0.0545

Alfa

AF:

0.0629

Hom.:

Bravo

AF:

0.0476

Asia WGS

AF:

0.0880

AC:

307

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 18, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Achromatopsia 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.038

DANN

Benign

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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