rs2055593

Variant names:

• chr2-98375650-G-A
• rs2055593
• NM_001298.3:c.102-2037G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• achromatopsia 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina, PanelApp Australia
• CNGA3-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• achromatopsia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CNGA3	NM_001298.3	c.102-2037G>A		intron_variant	Intron 2 of 7	ENST00000272602.7	NP_001289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGA3	ENST00000272602.7	c.102-2037G>A		intron_variant	Intron 2 of 7	1	NM_001298.3	ENSP00000272602.2
CNGA3	ENST00000436404.6	c.102-2037G>A		intron_variant	Intron 2 of 6	1		ENSP00000410070.2

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

African (AFR) AF: 0.397 AC: 16449 AN: 41452

American (AMR) AF: 0.412 AC: 6293 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1286 AN: 3470

East Asian (EAS) AF: 0.378 AC: 1954 AN: 5176

South Asian (SAS) AF: 0.202 AC: 976 AN: 4824

European-Finnish (FIN) AF: 0.203 AC: 2143 AN: 10582

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15788 AN: 68000

Other (OTH) AF: 0.323 AC: 682 AN: 2114

Alfa AF: 0.269 Hom.: 19124

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
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2055593; hg19: chr2-98992113;