chr13-37695539-C-T

Variant names:

• chr13-37695539-C-T
• rs10507457
• NM_016179.4:c.898-3204G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016179.4(TRPC4):​c.898-3204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0515 in 152,268 control chromosomes in the GnomAD database, including 280 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 0.051 (280 hom., cov: 32)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC4	NM_016179.4	c.898-3204G>A		intron_variant	Intron 3 of 10	ENST00000379705.8	NP_057263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC4	ENST00000379705.8	c.898-3204G>A		intron_variant	Intron 3 of 10	1	NM_016179.4	ENSP00000369027.4

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7842 AN: 152148 Hom.: 279 Cov.: 32

Gnomad AFR AF: 0.00956

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0545

Gnomad OTH AF: 0.0622

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

GnomAD4 genome AF: 0.0515 AC: 7840 AN: 152268 Hom.: 280 Cov.: 32 AF XY: 0.0544 AC XY: 4050 AN XY: 74464

African (AFR) AF: 0.00953 AC: 396 AN: 41556

American (AMR) AF: 0.0806 AC: 1233 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3472

East Asian (EAS) AF: 0.182 AC: 942 AN: 5170

South Asian (SAS) AF: 0.0891 AC: 430 AN: 4828

European-Finnish (FIN) AF: 0.0694 AC: 737 AN: 10614

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0545 AC: 3704 AN: 68008

Other (OTH) AF: 0.0616 AC: 130 AN: 2112

Alfa AF: 0.0506 Hom.: 246

Bravo AF: 0.0510

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.86
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10507457; hg19: chr13-38269676;