rs2991010

Positions:

• chr13-37716874-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.898-24539C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 152,068 control chromosomes in the GnomAD database, including 396 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 0.072 (396 hom., cov: 32)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC4	NM_016179.4	c.898-24539C>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.898-24539C>T		intron_variant		1	NM_016179.4	ENSP00000369027.4

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 10955 AN: 151950 Hom.: 390 Cov.: 32

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.0997

Gnomad FIN AF: 0.0788

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0643

Gnomad OTH AF: 0.0757

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

GnomAD4 genome AF: 0.0722 AC: 10979 AN: 152068 Hom.: 396 Cov.: 32 AF XY: 0.0721 AC XY: 5359 AN XY: 74316

Gnomad4 AFR AF: 0.0841

Gnomad4 AMR AF: 0.0735

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.0189

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0788

Gnomad4 NFE AF: 0.0643

Gnomad4 OTH AF: 0.0754

Alfa AF: 0.0709 Hom.: 538

Bravo AF: 0.0719

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.67

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: rs2991010; hg19: chr13-38291011;