chr13-37677502-G-A

Variant names:

• chr13-37677502-G-A
• rs7329459
• NM_016179.4:c.1235-3135C>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.1235-3135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,742 control chromosomes in the GnomAD database, including 4,873 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 0.24 (4873 hom., cov: 32)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016179.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC4	NM_016179.4	MANE Select	c.1235-3135C>T		intron	N/A	NP_057263.1
	TRPC4	NM_003306.3		c.1235-3135C>T		intron	N/A	NP_003297.1
	TRPC4	NM_001135955.3		c.1235-3135C>T		intron	N/A	NP_001129427.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC4	ENST00000379705.8	TSL:1 MANE Select	c.1235-3135C>T		intron	N/A	ENSP00000369027.4
	TRPC4	ENST00000625583.2	TSL:1	c.1235-3135C>T		intron	N/A	ENSP00000486109.1
	TRPC4	ENST00000358477.6	TSL:1	c.1235-3135C>T		intron	N/A	ENSP00000351264.2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37109 AN: 151624 Hom.: 4864 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.245 AC: 37140 AN: 151742 Hom.: 4873 Cov.: 32 AF XY: 0.251 AC XY: 18633 AN XY: 74130

African (AFR) AF: 0.261 AC: 10816 AN: 41366

American (AMR) AF: 0.251 AC: 3825 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3470

East Asian (EAS) AF: 0.535 AC: 2766 AN: 5168

South Asian (SAS) AF: 0.340 AC: 1635 AN: 4812

European-Finnish (FIN) AF: 0.253 AC: 2641 AN: 10450

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.208 AC: 14115 AN: 67924

Other (OTH) AF: 0.237 AC: 500 AN: 2106

Alfa AF: 0.218 Hom.: 5163

Bravo AF: 0.244

Asia WGS AF: 0.445 AC: 1544 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.62
DANN	Benign	0.51
PhyloP100		-0.54
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: rs7329459; hg19: chr13-38251639;