3-142727363-A-C

Variant names:

• chr3-142727363-A-C
• rs953239
• NM_001251845.2:c.172+2632A>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.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
• Publications: 17 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001251845.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC1	NM_001251845.2	MANE Select	c.172+2632A>C		intron	N/A	NP_001238774.1
	TRPC1	NM_003304.5		c.172+2632A>C		intron	N/A	NP_003295.1
	TRPC1	NM_001413362.1		c.172+2632A>C		intron	N/A	NP_001400291.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC1	ENST00000476941.6	TSL:1 MANE Select	c.172+2632A>C		intron	N/A	ENSP00000419313.1
	TRPC1	ENST00000273482.10	TSL:1	c.172+2632A>C		intron	N/A	ENSP00000273482.6
	TRPC1	ENST00000698238.1		c.481+2632A>C		intron	N/A	ENSP00000513620.1

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

African (AFR) AF: 0.602 AC: 24962 AN: 41460

American (AMR) AF: 0.328 AC: 5008 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3466

East Asian (EAS) AF: 0.343 AC: 1780 AN: 5182

South Asian (SAS) AF: 0.302 AC: 1453 AN: 4818

European-Finnish (FIN) AF: 0.420 AC: 4439 AN: 10560

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28245 AN: 67930

Other (OTH) AF: 0.435 AC: 921 AN: 2116

Alfa AF: 0.421 Hom.: 48251

Bravo AF: 0.450

Asia WGS AF: 0.352 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.88
PhyloP100		0.23
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: rs953239; hg19: chr3-142446205;