rs7319926

Variant names:

• chr13-37706293-A-G
• rs7319926
• NM_016179.4:c.898-13958T>C

Variant summary

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

The NM_016179.4(TRPC4):​c.898-13958T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,932 control chromosomes in the GnomAD database, including 19,886 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 0.51 (19886 hom., cov: 31)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 7 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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC4	NM_016179.4	c.898-13958T>C		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.898-13958T>C		intron_variant	Intron 3 of 10	1	NM_016179.4	ENSP00000369027.4

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77251 AN: 151814 Hom.: 19863 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.509 AC: 77312 AN: 151932 Hom.: 19886 Cov.: 31 AF XY: 0.504 AC XY: 37449 AN XY: 74244

African (AFR) AF: 0.509 AC: 21067 AN: 41412

American (AMR) AF: 0.457 AC: 6965 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2437 AN: 3472

East Asian (EAS) AF: 0.505 AC: 2602 AN: 5150

South Asian (SAS) AF: 0.449 AC: 2160 AN: 4816

European-Finnish (FIN) AF: 0.472 AC: 4979 AN: 10558

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35429 AN: 67952

Other (OTH) AF: 0.529 AC: 1119 AN: 2114

Alfa AF: 0.515 Hom.: 26647

Bravo AF: 0.508

Asia WGS AF: 0.435 AC: 1518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.0
DANN	Benign	0.79
PhyloP100		1.5
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: rs7319926; hg19: chr13-38280430; COSMIC: COSV59015784;