rs9548050

chr13-37789313-A-Gchr13-37789313-A-T

Variant summary

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

The NM_016179.4(TRPC4):c.-27-5953T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,982 control chromosomes in the GnomAD database, including 9,518 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 0.34 (9518 hom., cov: 32)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC4	NM_016179.4	c.-27-5953T>C		intron_variant		ENST00000379705.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC4	ENST00000379705.8	c.-27-5953T>C		intron_variant		1	NM_016179.4	P4

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50921 AN: 151864 Hom.: 9516 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.335 AC: 50927 AN: 151982 Hom.: 9518 Cov.: 32 AF XY: 0.335 AC XY: 24888 AN XY: 74282

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.321

Alfa AF: 0.393 Hom.: 16300

Bravo AF: 0.315

Asia WGS AF: 0.403 AC: 1394 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.7
Dann	Benign	0.42

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: rs9548050; hg19: chr13-38363450; COSMIC: COSV59015971;