rs7329459

chr13-37677502-G-A

Variant summary

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

The NM_016179.4(TRPC4):c.1235-3135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,742 control chromosomes in the GnomAD database, including 4,873 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 0.24 (4873 hom., cov: 32)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC4	NM_016179.4	c.1235-3135C>T		intron_variant		ENST00000379705.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC4	ENST00000379705.8	c.1235-3135C>T		intron_variant		1	NM_016179.4	P4

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37109 AN: 151624 Hom.: 4864 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.245 AC: 37140 AN: 151742 Hom.: 4873 Cov.: 32 AF XY: 0.251 AC XY: 18633 AN XY: 74130

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.237

Alfa AF: 0.213 Hom.: 3293

Bravo AF: 0.244

Asia WGS AF: 0.445 AC: 1544 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.62
Dann	Benign	0.51

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: rs7329459; hg19: chr13-38251639;