chr13-37646822-A-G

Variant names:

• chr13-37646822-A-G
• rs1535775
• NM_016179.4:c.2079+4443T>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.2079+4443T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,164 control chromosomes in the GnomAD database, including 41,404 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 0.73 (41404 hom., cov: 32)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778
• 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 (NFE) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC4	NM_016179.4	c.2079+4443T>C		intron_variant	Intron 8 of 10	ENST00000379705.8	NP_057263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC4	ENST00000379705.8	c.2079+4443T>C		intron_variant	Intron 8 of 10	1	NM_016179.4	ENSP00000369027.4

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111071 AN: 152046 Hom.: 41387 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.748

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

GnomAD4 genome AF: 0.730 AC: 111136 AN: 152164 Hom.: 41404 Cov.: 32 AF XY: 0.720 AC XY: 53587 AN XY: 74386

African (AFR) AF: 0.678 AC: 28146 AN: 41504

American (AMR) AF: 0.660 AC: 10082 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2917 AN: 3472

East Asian (EAS) AF: 0.300 AC: 1549 AN: 5166

South Asian (SAS) AF: 0.676 AC: 3262 AN: 4824

European-Finnish (FIN) AF: 0.749 AC: 7928 AN: 10590

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54652 AN: 68016

Other (OTH) AF: 0.746 AC: 1575 AN: 2112

Alfa AF: 0.759 Hom.: 5478

Bravo AF: 0.717

Asia WGS AF: 0.503 AC: 1751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.54
PhyloP100		-0.78
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: rs1535775; hg19: chr13-38220959;