rs1132030

chr3-142806016-G-Achr3-142806016-G-T

Variant summary

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

The NM_001251845.2(TRPC1):c.2163G>A(p.Arg721=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,611,862 control chromosomes in the GnomAD database, including 46,493 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 0.32 (11232 hom., cov: 32)
  • Exomes 𝑓: 0.20 (35261 hom.)
• Consequence: TRPC1 NM_001251845.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65

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=-0.53).
• BP7: Synonymous conserved (PhyloP=2.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC1	NM_001251845.2	c.2163G>A	p.Arg721=	synonymous_variant	13/13	ENST00000476941.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC1	ENST00000476941.6	c.2163G>A	p.Arg721=	synonymous_variant	13/13	1	NM_001251845.2	P1
TRPC1	ENST00000273482.10	c.2061G>A	p.Arg687=	synonymous_variant	12/12	1
TRPC1	ENST00000698238.1	c.2472G>A	p.Arg824=	synonymous_variant	13/13

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48963 AN: 151856 Hom.: 11194 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.276

GnomAD3 exomes AF: 0.222 AC: 55598 AN: 250202 Hom.: 8365 AF XY: 0.211 AC XY: 28568 AN XY: 135192

Gnomad AFR exome AF: 0.666

Gnomad AMR exome AF: 0.175

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.355

Gnomad SAS exome AF: 0.172

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.184

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.204 AC: 298177 AN: 1459888 Hom.: 35261 Cov.: 31 AF XY: 0.200 AC XY: 145508 AN XY: 726122

Gnomad4 AFR exome AF: 0.679

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.323 AC: 49055 AN: 151974 Hom.: 11232 Cov.: 32 AF XY: 0.318 AC XY: 23589 AN XY: 74258

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.284

Alfa AF: 0.219 Hom.: 3823

Bravo AF: 0.341

Asia WGS AF: 0.316 AC: 1100 AN: 3478

EpiCase AF: 0.187

EpiControl AF: 0.181

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	5.6
Dann	Benign	0.81

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: rs1132030; hg19: chr3-142524858; COSMIC: COSV56429297; COSMIC: COSV56429297;