NM_001251845.2:c.633-6323T>C

Variant names:

• chr3-142771309-T-C
• rs7638459
• NM_001251845.2:c.633-6323T>C

Variant summary

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

The NM_001251845.2(TRPC1):​c.633-6323T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,058 control chromosomes in the GnomAD database, including 12,704 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 0.35 (12704 hom., cov: 32)
• Consequence: TRPC1 NM_001251845.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC1	NM_001251845.2	c.633-6323T>C		intron_variant	Intron 4 of 12	ENST00000476941.6	NP_001238774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC1	ENST00000476941.6	c.633-6323T>C		intron_variant	Intron 4 of 12	1	NM_001251845.2	ENSP00000419313.1
TRPC1	ENST00000273482.10	c.531-6323T>C		intron_variant	Intron 3 of 11	1		ENSP00000273482.6
TRPC1	ENST00000698238.1	c.942-6323T>C		intron_variant	Intron 4 of 12			ENSP00000513620.1
TRPC1	ENST00000460401.1	n.*175-6323T>C		intron_variant	Intron 2 of 2	3		ENSP00000418708.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52846 AN: 151940 Hom.: 12653 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.348 AC: 52955 AN: 152058 Hom.: 12704 Cov.: 32 AF XY: 0.343 AC XY: 25481 AN XY: 74348

African (AFR) AF: 0.690 AC: 28572 AN: 41430

American (AMR) AF: 0.215 AC: 3281 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3466

East Asian (EAS) AF: 0.432 AC: 2234 AN: 5176

South Asian (SAS) AF: 0.212 AC: 1019 AN: 4816

European-Finnish (FIN) AF: 0.202 AC: 2141 AN: 10586

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

European-Non Finnish (NFE) AF: 0.212 AC: 14407 AN: 67988

Other (OTH) AF: 0.303 AC: 641 AN: 2116

Alfa AF: 0.298 Hom.: 1538

Bravo AF: 0.365

Asia WGS AF: 0.348 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.76
DANN	Benign	0.36
PhyloP100		-1.0
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: rs7638459; hg19: chr3-142490151; COSMIC: COSV107262526;