rs1132030

Variant names:

• chr3-142806016-G-A
• rs1132030
• NM_001251845.2:c.2163G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-142806016-G-A
• chr3-142806016-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001251845.2(TRPC1):​c.2163G>A​(p.Arg721Arg) 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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TRPC1	NM_001251845.2	c.2163G>A	p.Arg721Arg	synonymous_variant	Exon 13 of 13	ENST00000476941.6	NP_001238774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC1	ENST00000476941.6	c.2163G>A	p.Arg721Arg	synonymous_variant	Exon 13 of 13	1	NM_001251845.2	ENSP00000419313.1
TRPC1	ENST00000273482.10	c.2061G>A	p.Arg687Arg	synonymous_variant	Exon 12 of 12	1		ENSP00000273482.6
TRPC1	ENST00000698238.1	c.2472G>A	p.Arg824Arg	synonymous_variant	Exon 13 of 13			ENSP00000513620.1

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

GnomAD2 exomes AF: 0.222 AC: 55598 AN: 250202 AF XY: 0.211

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 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

African (AFR) AF: 0.679 AC: 22675 AN: 33390

American (AMR) AF: 0.182 AC: 8100 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2969 AN: 26112

East Asian (EAS) AF: 0.313 AC: 12391 AN: 39616

South Asian (SAS) AF: 0.176 AC: 15096 AN: 85968

European-Finnish (FIN) AF: 0.178 AC: 9508 AN: 53388

Middle Eastern (MID) AF: 0.159 AC: 915 AN: 5756

European-Non Finnish (NFE) AF: 0.192 AC: 212865 AN: 1110772

Other (OTH) AF: 0.226 AC: 13658 AN: 60308

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

African (AFR) AF: 0.658 AC: 27236 AN: 41418

American (AMR) AF: 0.205 AC: 3126 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 404 AN: 3466

East Asian (EAS) AF: 0.367 AC: 1900 AN: 5174

South Asian (SAS) AF: 0.181 AC: 870 AN: 4818

European-Finnish (FIN) AF: 0.179 AC: 1893 AN: 10568

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12814 AN: 67952

Other (OTH) AF: 0.284 AC: 599 AN: 2112

Alfa AF: 0.225 Hom.: 4709

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
PhyloP100		2.6
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: rs1132030; hg19: chr3-142524858; COSMIC: COSV56429297; COSMIC: COSV56429297;