rs2033912

Variant names:

• chr3-142797525-A-T
• rs2033912
• NM_001251845.2:c.1581+4558A>T

Variant summary

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

The NM_001251845.2(TRPC1):​c.1581+4558A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,920 control chromosomes in the GnomAD database, including 13,667 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 0.36 (13667 hom., cov: 32)
• Consequence: TRPC1 NM_001251845.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC1	NM_001251845.2	c.1581+4558A>T		intron_variant	Intron 9 of 12	ENST00000476941.6	NP_001238774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC1	ENST00000476941.6	c.1581+4558A>T		intron_variant	Intron 9 of 12	1	NM_001251845.2	ENSP00000419313.1
TRPC1	ENST00000273482.10	c.1479+4558A>T		intron_variant	Intron 8 of 11	1		ENSP00000273482.6
TRPC1	ENST00000698238.1	c.1890+4558A>T		intron_variant	Intron 9 of 12			ENSP00000513620.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54251 AN: 151802 Hom.: 13611 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.302

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.358 AC: 54368 AN: 151920 Hom.: 13667 Cov.: 32 AF XY: 0.352 AC XY: 26149 AN XY: 74274

African (AFR) AF: 0.723 AC: 29946 AN: 41404

American (AMR) AF: 0.217 AC: 3311 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3464

East Asian (EAS) AF: 0.431 AC: 2222 AN: 5154

South Asian (SAS) AF: 0.212 AC: 1023 AN: 4818

European-Finnish (FIN) AF: 0.202 AC: 2134 AN: 10584

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

European-Non Finnish (NFE) AF: 0.212 AC: 14419 AN: 67936

Other (OTH) AF: 0.310 AC: 654 AN: 2110

Alfa AF: 0.299 Hom.: 1188

Bravo AF: 0.376

Asia WGS AF: 0.351 AC: 1223 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.0
DANN	Benign	0.83
PhyloP100		-0.070
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: rs2033912; hg19: chr3-142516367;