rs4259003

Variant names:

• chr3-142804713-G-A
• rs4259003
• NM_001251845.2:c.2154+83G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001251845.2(TRPC1):​c.2154+83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,331,468 control chromosomes in the GnomAD database, including 37,072 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 0.31 (10321 hom., cov: 32)
  • Exomes 𝑓: 0.20 (26751 hom.)
• Consequence: TRPC1 NM_001251845.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC1	NM_001251845.2	c.2154+83G>A		intron_variant	Intron 12 of 12	ENST00000476941.6	NP_001238774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC1	ENST00000476941.6	c.2154+83G>A		intron_variant	Intron 12 of 12	1	NM_001251845.2	ENSP00000419313.1
TRPC1	ENST00000273482.10	c.2052+83G>A		intron_variant	Intron 11 of 11	1		ENSP00000273482.6
TRPC1	ENST00000698238.1	c.2463+83G>A		intron_variant	Intron 12 of 12			ENSP00000513620.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47197 AN: 151936 Hom.: 10302 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.200 AC: 236058 AN: 1179414 Hom.: 26751 AF XY: 0.196 AC XY: 115462 AN XY: 588312

African (AFR) AF: 0.651 AC: 16969 AN: 26052

American (AMR) AF: 0.182 AC: 5140 AN: 28290

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2133 AN: 19216

East Asian (EAS) AF: 0.234 AC: 8502 AN: 36282

South Asian (SAS) AF: 0.155 AC: 9780 AN: 63256

European-Finnish (FIN) AF: 0.179 AC: 8650 AN: 48406

Middle Eastern (MID) AF: 0.154 AC: 672 AN: 4360

European-Non Finnish (NFE) AF: 0.192 AC: 173319 AN: 903398

Other (OTH) AF: 0.217 AC: 10893 AN: 50154

GnomAD4 genome AF: 0.311 AC: 47257 AN: 152054 Hom.: 10321 Cov.: 32 AF XY: 0.305 AC XY: 22644 AN XY: 74328

African (AFR) AF: 0.631 AC: 26178 AN: 41468

American (AMR) AF: 0.198 AC: 3021 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3466

East Asian (EAS) AF: 0.277 AC: 1435 AN: 5178

South Asian (SAS) AF: 0.154 AC: 740 AN: 4818

European-Finnish (FIN) AF: 0.179 AC: 1892 AN: 10562

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

European-Non Finnish (NFE) AF: 0.189 AC: 12814 AN: 67976

Other (OTH) AF: 0.267 AC: 562 AN: 2108

Alfa AF: 0.215 Hom.: 2430

Bravo AF: 0.327

Asia WGS AF: 0.251 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.82
PhyloP100		0.14
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: rs4259003; hg19: chr3-142523555; COSMIC: COSV56423706; COSMIC: COSV56423706;