rs3821647

Positions:

• chr3-142804507-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001251845.2(TRPC1):​c.2031G>A​(p.Thr677=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,613,014 control chromosomes in the GnomAD database, including 28,740 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 0.19 (2813 hom., cov: 32)
  • Exomes 𝑓: 0.19 (25927 hom.)
• Consequence: TRPC1 NM_001251845.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

Genes affected

TRPC1 (HGNC:12333): (transient receptor potential cation channel subfamily C member 1) The protein encoded by this gene is a membrane protein that can form a non-selective channel permeable to calcium and other cations. The encoded protein appears to be induced to form channels by a receptor tyrosine kinase-activated phosphatidylinositol second messenger system and also by depletion of intracellular calcium stores. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=-1.53 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC1	NM_001251845.2	c.2031G>A	p.Thr677=	synonymous_variant	12/13	ENST00000476941.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC1	ENST00000476941.6	c.2031G>A	p.Thr677=	synonymous_variant	12/13	1	NM_001251845.2	P1
TRPC1	ENST00000273482.10	c.1929G>A	p.Thr643=	synonymous_variant	11/12	1
TRPC1	ENST00000698238.1	c.2340G>A	p.Thr780=	synonymous_variant	12/13

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28847 AN: 151866 Hom.: 2808 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.182

GnomAD3 exomes AF: 0.178 AC: 44754 AN: 250810 Hom.: 4327 AF XY: 0.176 AC XY: 23871 AN XY: 135548

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.269

Gnomad SAS exome AF: 0.145

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.182

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.187 AC: 272543 AN: 1461030 Hom.: 25927 Cov.: 32 AF XY: 0.184 AC XY: 133614 AN XY: 726822

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.233

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.190 AC: 28871 AN: 151984 Hom.: 2813 Cov.: 32 AF XY: 0.188 AC XY: 13988 AN XY: 74256

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.182

Alfa AF: 0.182 Hom.: 3483

Bravo AF: 0.191

Asia WGS AF: 0.223 AC: 776 AN: 3478

EpiCase AF: 0.185

EpiControl AF: 0.178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	2.1
DANN	Benign	0.80

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: rs3821647; hg19: chr3-142523349; COSMIC: COSV56422960; COSMIC: COSV56422960;