rs10161932

chr13-37636794-C-T

Variant summary

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

The NM_016179.4(TRPC4):c.*109G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,333,458 control chromosomes in the GnomAD database, including 37,396 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 0.22 (4338 hom., cov: 32)
  • Exomes 𝑓: 0.23 (33058 hom.)
• Consequence: TRPC4 NM_016179.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830

Genes affected

TRPC4 (HGNC:12336): (transient receptor potential cation channel subfamily C member 4) This gene encodes a member of the canonical subfamily of transient receptor potential cation channels. The encoded protein forms a non-selective calcium-permeable cation channel that is activated by Gq-coupled receptors and tyrosine kinases, and plays a role in multiple processes including endothelial permeability, vasodilation, neurotransmitter release and cell proliferation. Single nucleotide polymorphisms in this gene may be associated with generalized epilepsy with photosensitivity. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC4	NM_016179.4	c.*109G>A		3_prime_UTR_variant	11/11	ENST00000379705.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC4	ENST00000379705.8	c.*109G>A		3_prime_UTR_variant	11/11	1	NM_016179.4	P4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33287 AN: 148300 Hom.: 4336 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.225 AC: 266937 AN: 1185040 Hom.: 33058 Cov.: 19 AF XY: 0.226 AC XY: 131532 AN XY: 581228

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.672

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.224 AC: 33307 AN: 148418 Hom.: 4338 Cov.: 32 AF XY: 0.234 AC XY: 16988 AN XY: 72532

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.684

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.215

Alfa AF: 0.195 Hom.: 2100

Bravo AF: 0.219

Asia WGS AF: 0.432 AC: 1501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	0.94
Dann	Benign	0.65

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: rs10161932; hg19: chr13-38210931; COSMIC: COSV59020271; COSMIC: COSV59020271;