rs7338118

Positions:

• chr13-37654319-A-C

Variant summary

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

The NM_016179.4(TRPC4):​c.1884+769T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,080 control chromosomes in the GnomAD database, including 5,341 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 0.25 (5341 hom., cov: 32)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC4	NM_016179.4	c.1884+769T>G		intron_variant		ENST00000379705.8	NP_057263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC4	ENST00000379705.8	c.1884+769T>G		intron_variant		1	NM_016179.4	ENSP00000369027.4

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37734 AN: 151960 Hom.: 5329 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.248 AC: 37777 AN: 152080 Hom.: 5341 Cov.: 32 AF XY: 0.258 AC XY: 19146 AN XY: 74336

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.245

Alfa AF: 0.227 Hom.: 526

Bravo AF: 0.257

Asia WGS AF: 0.495 AC: 1717 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.8
DANN	Benign	0.83

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: rs7338118; hg19: chr13-38228456;