rs58990587

chr2-98377846-T-Achr2-98377846-T-Cchr2-98377846-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001298.3(CNGA3):c.215+46T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,542,812 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0090 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00090 (18 hom.)
• Consequence: CNGA3 NM_001298.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.969

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-98377846-T-A is Benign according to our data. Variant chr2-98377846-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1254794.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00901 (1372/152212) while in subpopulation AFR AF= 0.0307 (1273/41524). AF 95% confidence interval is 0.0293. There are 17 homozygotes in gnomad4. There are 625 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNGA3	NM_001298.3	c.215+46T>A		intron_variant		ENST00000272602.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNGA3	ENST00000272602.7	c.215+46T>A		intron_variant		1	NM_001298.3	A1
CNGA3	ENST00000436404.6	c.215+46T>A		intron_variant		1		P4
CNGA3	ENST00000409937.1	n.203+46T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00895 AC: 1361 AN: 152094 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

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: 0.0000294

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00230 AC: 427 AN: 185940 Hom.: 3 AF XY: 0.00182 AC XY: 183 AN XY: 100404

Gnomad AFR exome AF: 0.0328

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000169

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000505

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000900 AC: 1252 AN: 1390600 Hom.: 18 Cov.: 22 AF XY: 0.000801 AC XY: 552 AN XY: 689330

Gnomad4 AFR exome AF: 0.0319

Gnomad4 AMR exome AF: 0.00185

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000150

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00213

GnomAD4 genome AF: 0.00901 AC: 1372 AN: 152212 Hom.: 17 Cov.: 32 AF XY: 0.00840 AC XY: 625 AN XY: 74438

Gnomad4 AFR AF: 0.0307

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.000226 Hom.: 56

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.2
Dann	Benign	0.26

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: rs58990587; hg19: chr2-98994309;