rs953239

Positions:

• chr3-142727363-A-C
• chr3-142727363-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001251845.2(TRPC1):​c.172+2632A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,006 control chromosomes in the GnomAD database, including 16,274 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 0.45 (16274 hom., cov: 32)
• Consequence: TRPC1 NM_001251845.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC1	NM_001251845.2	c.172+2632A>C		intron_variant		ENST00000476941.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC1	ENST00000476941.6	c.172+2632A>C		intron_variant		1	NM_001251845.2	P1
TRPC1	ENST00000273482.10	c.172+2632A>C		intron_variant		1
TRPC1	ENST00000698238.1	c.481+2632A>C		intron_variant
TRPC1	ENST00000460401.1	c.167+2632A>C		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68499 AN: 151888 Hom.: 16255 Cov.: 32

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.451 AC: 68559 AN: 152006 Hom.: 16274 Cov.: 32 AF XY: 0.446 AC XY: 33115 AN XY: 74276

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.435

Alfa AF: 0.411 Hom.: 16935

Bravo AF: 0.450

Asia WGS AF: 0.352 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.88

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: rs953239; hg19: chr3-142446205;