13-37789313-A-G

Variant names:

• chr13-37789313-A-G
• rs9548050
• NM_016179.4:c.-27-5953T>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.-27-5953T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,982 control chromosomes in the GnomAD database, including 9,518 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 0.34 (9518 hom., cov: 32)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC4	NM_016179.4	c.-27-5953T>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.-27-5953T>C		intron_variant	Intron 1 of 10	1	NM_016179.4	ENSP00000369027.4

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50921 AN: 151864 Hom.: 9516 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.335 AC: 50927 AN: 151982 Hom.: 9518 Cov.: 32 AF XY: 0.335 AC XY: 24888 AN XY: 74282

African (AFR) AF: 0.189 AC: 7825 AN: 41508

American (AMR) AF: 0.284 AC: 4331 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3464

East Asian (EAS) AF: 0.374 AC: 1929 AN: 5156

South Asian (SAS) AF: 0.470 AC: 2263 AN: 4816

European-Finnish (FIN) AF: 0.375 AC: 3961 AN: 10558

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28572 AN: 67922

Other (OTH) AF: 0.321 AC: 679 AN: 2112

Alfa AF: 0.370 Hom.: 23183

Bravo AF: 0.315

Asia WGS AF: 0.403 AC: 1394 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.42
PhyloP100		0.011
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: rs9548050; hg19: chr13-38363450; COSMIC: COSV59015971;