chr13-37668053-G-A

Position:

• chr13-37668053-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.1375-4324C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,134 control chromosomes in the GnomAD database, including 1,754 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 0.15 (1754 hom., cov: 32)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC4	NM_016179.4	c.1375-4324C>T		intron_variant		ENST00000379705.8	NP_057263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC4	ENST00000379705.8	c.1375-4324C>T		intron_variant		1	NM_016179.4	ENSP00000369027	P4

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22170 AN: 152014 Hom.: 1751 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.146 AC: 22192 AN: 152134 Hom.: 1754 Cov.: 32 AF XY: 0.151 AC XY: 11232 AN XY: 74370

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.149

Alfa AF: 0.101 Hom.: 421

Bravo AF: 0.147

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.66

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: rs10507456; hg19: chr13-38242190; COSMIC: COSV59014748;