rs2055593

Positions:

• chr2-98375650-G-A
• chr2-98375650-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001298.3(CNGA3):​c.102-2037G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,106 control chromosomes in the GnomAD database, including 7,511 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7511 hom., cov: 33)
• Consequence: CNGA3 NM_001298.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNGA3	NM_001298.3	c.102-2037G>A		intron_variant		ENST00000272602.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNGA3	ENST00000272602.7	c.102-2037G>A		intron_variant		1	NM_001298.3	A1
CNGA3	ENST00000436404.6	c.102-2037G>A		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45884 AN: 151988 Hom.: 7477 Cov.: 33

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.326

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.302 AC: 45964 AN: 152106 Hom.: 7511 Cov.: 33 AF XY: 0.302 AC XY: 22454 AN XY: 74380

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.323

Alfa AF: 0.259 Hom.: 11412

Bravo AF: 0.328

Asia WGS AF: 0.305 AC: 1059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.15
DANN	Benign	0.22

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: rs2055593; hg19: chr2-98992113;