ENST00000436404.6:c.-286C>T

Variant names:

• chr2-98346286-C-T
• rs13408372
• ENST00000436404.6:c.-286C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.54
• 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: Illumina, G2P, Labcorp Genetics (formerly Invitae)
• 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

ENSG00000222000 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 337649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000436404.6. 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.-286C>T		upstream_gene	N/A	NP_001289.1	Q16281-1
	CNGA3	NM_001079878.2		c.-286C>T		upstream_gene	N/A	NP_001073347.1	Q16281-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGA3	ENST00000436404.6	TSL:1	c.-286C>T		5_prime_UTR	Exon 1 of 7	ENSP00000410070.2	Q16281-2
	CNGA3	ENST00000853268.1		c.-286C>T		5_prime_UTR	Exon 1 of 9	ENSP00000523327.1
	CNGA3	ENST00000853267.1		c.-286C>T		5_prime_UTR	Exon 1 of 8	ENSP00000523326.1

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

African (AFR) AF: 0.0696 AC: 500 AN: 7182

American (AMR) AF: 0.201 AC: 1496 AN: 7428

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 503 AN: 9230

East Asian (EAS) AF: 0.190 AC: 4352 AN: 22888

South Asian (SAS) AF: 0.0574 AC: 172 AN: 2998

European-Finnish (FIN) AF: 0.0325 AC: 678 AN: 20830

Middle Eastern (MID) AF: 0.0293 AC: 38 AN: 1296

European-Non Finnish (NFE) AF: 0.0469 AC: 7419 AN: 158130

Other (OTH) AF: 0.0706 AC: 1155 AN: 16362

GnomAD4 genome AF: 0.0681 AC: 10367 AN: 152284 Hom.: 525 Cov.: 32 AF XY: 0.0700 AC XY: 5215 AN XY: 74482

African (AFR) AF: 0.0707 AC: 2939 AN: 41566

American (AMR) AF: 0.166 AC: 2539 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3472

East Asian (EAS) AF: 0.182 AC: 939 AN: 5160

South Asian (SAS) AF: 0.0597 AC: 288 AN: 4826

European-Finnish (FIN) AF: 0.0274 AC: 291 AN: 10628

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0445 AC: 3027 AN: 68014

Other (OTH) AF: 0.0728 AC: 154 AN: 2114

Alfa AF: 0.0599 Hom.: 423

Bravo AF: 0.0822

Asia WGS AF: 0.0940 AC: 325 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Achromatopsia 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		1.5
PromoterAI		-0.020	Neutral
Mutation Taster		=300/0	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: rs13408372; hg19: chr2-98962749;