rs58990587

Variant names:

• chr2-98377846-T-A
• rs58990587
• NM_001298.3:c.215+46T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-98377846-T-A
• chr2-98377846-T-G
• chr2-98377846-T-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Illumina, Labcorp Genetics (formerly Invitae), G2P
• 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001298.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGA3	NM_001298.3	MANE Select	c.215+46T>A		intron	N/A	NP_001289.1	Q16281-1
	CNGA3	NM_001079878.2		c.215+46T>A		intron	N/A	NP_001073347.1	Q16281-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGA3	ENST00000272602.7	TSL:1 MANE Select	c.215+46T>A		intron	N/A	ENSP00000272602.2	Q16281-1
	CNGA3	ENST00000436404.6	TSL:1	c.215+46T>A		intron	N/A	ENSP00000410070.2	Q16281-2
	CNGA3	ENST00000853268.1		c.215+46T>A		intron	N/A	ENSP00000523327.1

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

GnomAD2 exomes AF: 0.00230 AC: 427 AN: 185940 AF XY: 0.00182

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 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

African (AFR) AF: 0.0319 AC: 1019 AN: 31956

American (AMR) AF: 0.00185 AC: 72 AN: 38984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24534

East Asian (EAS) AF: 0.00 AC: 0 AN: 38260

South Asian (SAS) AF: 0.000150 AC: 12 AN: 80142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50712

Middle Eastern (MID) AF: 0.000713 AC: 3 AN: 4208

European-Non Finnish (NFE) AF: 0.0000216 AC: 23 AN: 1064152

Other (OTH) AF: 0.00213 AC: 123 AN: 57652

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

African (AFR) AF: 0.0307 AC: 1273 AN: 41524

American (AMR) AF: 0.00523 AC: 80 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68004

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.000132 Hom.: 107

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
DANN	Benign	0.26
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs58990587;

hg19: chr2-98994309;