chr13-37777669-C-T

Position:

• chr13-37777669-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.378+5287G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,750 control chromosomes in the GnomAD database, including 15,852 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 (15852 hom., cov: 32)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC4	NM_016179.4	c.378+5287G>A		intron_variant		ENST00000379705.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC4	ENST00000379705.8	c.378+5287G>A		intron_variant		1	NM_016179.4	P4

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68689 AN: 151632 Hom.: 15848 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.453 AC: 68718 AN: 151750 Hom.: 15852 Cov.: 32 AF XY: 0.450 AC XY: 33364 AN XY: 74140

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.441

Alfa AF: 0.464 Hom.: 2008

Bravo AF: 0.452

Asia WGS AF: 0.330 AC: 1152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.20

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: rs1333373; hg19: chr13-38351806; COSMIC: COSV59015941;