2-98346286-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000436404.6(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 ENST00000436404.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.54

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNGA3	ENST00000436404.6	c.-286C>T		5_prime_UTR_variant	1/7	1		P4
	ENST00000454230.1	n.191+9529G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0680 AC: 10341 AN: 152166 Hom.: 524 Cov.: 32

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.: 0 AF XY: 0.0657 AC XY: 8204 AN XY: 124896

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.: 32 AF XY: 0.0700 AC XY: 5215 AN XY: 74482

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:1

Revision: criteria provided, single submitter

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	12
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

Other links and lift over

dbSNP: rs13408372; hg19: chr2-98962749;