Variant chr2-98346286-C-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 ENST00000436404(CNGA3):c.-286C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 398,628 control chromosomes in the GnomAD database, including 1,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 525 hom., cov: 32)

Exomes 𝑓: 0.066 ( 868 hom. )

Consequence

CNGA3
ENST00000436404 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.54

Variant links:

Genes affected

CNGA3 (HGNC:2150): (cyclic nucleotide gated channel subunit alpha 3) This gene encodes a member of the cyclic nucleotide-gated cation channel protein family which is required for normal vision and olfactory signal transduction. Mutations in this gene are associated with achromatopsia (rod monochromacy) and color blindness. Two alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

CNGA3 links:

(HGNC:):

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=-0.73).

BP6

Variant 2-98346286-C-T is Benign according to our data. Variant chr2-98346286-C-T is described in ClinVar as [Benign]. Clinvar id is 337649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-98346286-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
	use as main transcript	n.98346286C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGA3	ENST00000436404 linkuse as main transcript	c.-286C>T		5_prime_UTR_variant	1/7	1		ENSP00000410070.2		Q16281-2
ENSG00000222000	ENST00000454230.1 linkuse as main transcript	n.191+9529G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0680

AC:

10341

AN:

152166

Hom.:

524

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0706

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.0533

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.0598

Gnomad FIN

AF:

0.0274

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0445

Gnomad OTH

AF:

0.0727

GnomAD4 exome

AF:

0.0662

AC:

16313

AN:

246344

Hom.:

868

Cov.:

AF XY:

0.0657

AC XY:

8204

AN XY:

124896

show subpopulations

Gnomad4 AFR exome

AF:

0.0696

Gnomad4 AMR exome

AF:

0.201

Gnomad4 ASJ exome

AF:

0.0545

Gnomad4 EAS exome

AF:

0.190

Gnomad4 SAS exome

AF:

0.0574

Gnomad4 FIN exome

AF:

0.0325

Gnomad4 NFE exome

AF:

0.0469

Gnomad4 OTH exome

AF:

0.0706

GnomAD4 genome

AF:

0.0681

AC:

10367

AN:

152284

Hom.:

525

Cov.:

AF XY:

0.0700

AC XY:

5215

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0707

Gnomad4 AMR

AF:

0.166

Gnomad4 ASJ

AF:

0.0533

Gnomad4 EAS

AF:

0.182

Gnomad4 SAS

AF:

0.0597

Gnomad4 FIN

AF:

0.0274

Gnomad4 NFE

AF:

0.0445

Gnomad4 OTH

AF:

0.0728

Alfa

AF:

0.0536

Hom.:

215

Bravo

AF:

0.0822

Asia WGS

AF:

0.0940

AC:

325

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Achromatopsia 2

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.88

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