rs2991010

Variant names:

• chr13-37716874-G-A
• rs2991010
• NM_016179.4:c.898-24539C>T

Variant summary

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

The NM_016179.4(TRPC4):​c.898-24539C>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
• 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=-0.8).
• 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 rank	MANE	Protein	UniProt
TRPC4	NM_016179.4	c.898-24539C>T		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.898-24539C>T		intron_variant	Intron 3 of 10	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

African (AFR) AF: 0.0841 AC: 3488 AN: 41470

American (AMR) AF: 0.0735 AC: 1121 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 301 AN: 3470

East Asian (EAS) AF: 0.0189 AC: 98 AN: 5174

South Asian (SAS) AF: 0.101 AC: 486 AN: 4820

European-Finnish (FIN) AF: 0.0788 AC: 834 AN: 10578

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0643 AC: 4373 AN: 67988

Other (OTH) AF: 0.0754 AC: 159 AN: 2108

Alfa AF: 0.0702 Hom.: 762

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
PhyloP100		0.44
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: rs2991010; hg19: chr13-38291011;