NM_016179.4:c.*109G>A

Variant names:

• chr13-37636794-C-T
• rs10161932
• NM_016179.4:c.*109G>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.*109G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,333,458 control chromosomes in the GnomAD database, including 37,396 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 0.22 (4338 hom., cov: 32)
  • Exomes 𝑓: 0.23 (33058 hom.)
• Consequence: TRPC4 NM_016179.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 6 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]

ENSG00000297050 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 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.*109G>A		3_prime_UTR	Exon 11 of 11	NP_057263.1
	TRPC4	NM_003306.3		c.*109G>A		3_prime_UTR	Exon 11 of 11	NP_003297.1
	TRPC4	NM_001135955.3		c.*109G>A		3_prime_UTR	Exon 12 of 12	NP_001129427.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC4	ENST00000379705.8	TSL:1 MANE Select	c.*109G>A		3_prime_UTR	Exon 11 of 11	ENSP00000369027.4
	TRPC4	ENST00000957123.1		c.*109G>A		3_prime_UTR	Exon 12 of 12	ENSP00000627182.1
	TRPC4	ENST00000957124.1		c.*109G>A		3_prime_UTR	Exon 11 of 11	ENSP00000627183.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33287 AN: 148300 Hom.: 4336 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.225 AC: 266937 AN: 1185040 Hom.: 33058 Cov.: 19 AF XY: 0.226 AC XY: 131532 AN XY: 581228

African (AFR) AF: 0.190 AC: 5175 AN: 27210

American (AMR) AF: 0.279 AC: 6816 AN: 24400

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 2879 AN: 18422

East Asian (EAS) AF: 0.672 AC: 25409 AN: 37814

South Asian (SAS) AF: 0.288 AC: 16321 AN: 56648

European-Finnish (FIN) AF: 0.251 AC: 10376 AN: 41376

Middle Eastern (MID) AF: 0.188 AC: 617 AN: 3276

European-Non Finnish (NFE) AF: 0.202 AC: 187400 AN: 926106

Other (OTH) AF: 0.240 AC: 11944 AN: 49788

GnomAD4 genome AF: 0.224 AC: 33307 AN: 148418 Hom.: 4338 Cov.: 32 AF XY: 0.234 AC XY: 16988 AN XY: 72532

African (AFR) AF: 0.181 AC: 7372 AN: 40622

American (AMR) AF: 0.270 AC: 4025 AN: 14918

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 535 AN: 3408

East Asian (EAS) AF: 0.684 AC: 3519 AN: 5144

South Asian (SAS) AF: 0.304 AC: 1403 AN: 4610

European-Finnish (FIN) AF: 0.258 AC: 2665 AN: 10312

Middle Eastern (MID) AF: 0.182 AC: 51 AN: 280

European-Non Finnish (NFE) AF: 0.199 AC: 13177 AN: 66210

Other (OTH) AF: 0.215 AC: 439 AN: 2046

Alfa AF: 0.194 Hom.: 2462

Bravo AF: 0.219

Asia WGS AF: 0.432 AC: 1501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.94
DANN	Benign	0.65
PhyloP100		0.083
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: rs10161932; hg19: chr13-38210931; COSMIC: COSV59020271; COSMIC: COSV59020271;