rs7319926

chr13-37706293-A-G

Variant summary

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

The NM_016179.4(TRPC4):c.898-13958T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,932 control chromosomes in the GnomAD database, including 19,886 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 0.51 (19886 hom., cov: 31)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC4	NM_016179.4	c.898-13958T>C		intron_variant		ENST00000379705.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC4	ENST00000379705.8	c.898-13958T>C		intron_variant		1	NM_016179.4	P4

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77251 AN: 151814 Hom.: 19863 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.509 AC: 77312 AN: 151932 Hom.: 19886 Cov.: 31 AF XY: 0.504 AC XY: 37449 AN XY: 74244

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.529

Alfa AF: 0.517 Hom.: 20410

Bravo AF: 0.508

Asia WGS AF: 0.435 AC: 1518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	8.0
Dann	Benign	0.79

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: rs7319926; hg19: chr13-38280430; COSMIC: COSV59015784;