chr13-37867711-C-G

Variant names:

• chr13-37867711-C-G
• rs10507461
• NM_016179.4:c.-28+1884G>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.-28+1884G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0176 in 152,112 control chromosomes in the GnomAD database, including 54 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 0.018 (54 hom., cov: 33)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC4	NM_016179.4	c.-28+1884G>C		intron_variant	Intron 1 of 10	ENST00000379705.8	NP_057263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC4	ENST00000379705.8	c.-28+1884G>C		intron_variant	Intron 1 of 10	1	NM_016179.4	ENSP00000369027.4

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2680 AN: 151994 Hom.: 54 Cov.: 33

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00722

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0421

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00755

Gnomad OTH AF: 0.0125

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

GnomAD4 genome AF: 0.0176 AC: 2676 AN: 152112 Hom.: 54 Cov.: 33 AF XY: 0.0181 AC XY: 1344 AN XY: 74368

African (AFR) AF: 0.0310 AC: 1286 AN: 41548

American (AMR) AF: 0.00406 AC: 62 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00722 AC: 25 AN: 3462

East Asian (EAS) AF: 0.103 AC: 535 AN: 5186

South Asian (SAS) AF: 0.0419 AC: 202 AN: 4822

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10604

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00756 AC: 513 AN: 67896

Other (OTH) AF: 0.0119 AC: 25 AN: 2104

Alfa AF: 0.0132 Hom.: 4

Bravo AF: 0.0178

Asia WGS AF: 0.0620 AC: 212 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.81
DANN	Benign	0.45
PhyloP100		-0.14
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: rs10507461; hg19: chr13-38441848;