rs1333373

Variant names:

• chr13-37777669-C-T
• rs1333373
• NM_016179.4:c.378+5287G>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.378+5287G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,750 control chromosomes in the GnomAD database, including 15,852 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 0.45 (15852 hom., cov: 32)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 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.378+5287G>A		intron	N/A	NP_057263.1
	TRPC4	NM_003306.3		c.378+5287G>A		intron	N/A	NP_003297.1
	TRPC4	NM_001135955.3		c.378+5287G>A		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.378+5287G>A		intron	N/A	ENSP00000369027.4
	TRPC4	ENST00000625583.2	TSL:1	c.378+5287G>A		intron	N/A	ENSP00000486109.1
	TRPC4	ENST00000358477.6	TSL:1	c.378+5287G>A		intron	N/A	ENSP00000351264.2

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68689 AN: 151632 Hom.: 15848 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.453 AC: 68718 AN: 151750 Hom.: 15852 Cov.: 32 AF XY: 0.450 AC XY: 33364 AN XY: 74140

African (AFR) AF: 0.495 AC: 20484 AN: 41374

American (AMR) AF: 0.371 AC: 5657 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1896 AN: 3468

East Asian (EAS) AF: 0.219 AC: 1123 AN: 5132

South Asian (SAS) AF: 0.442 AC: 2130 AN: 4818

European-Finnish (FIN) AF: 0.414 AC: 4375 AN: 10558

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31443 AN: 67866

Other (OTH) AF: 0.441 AC: 925 AN: 2098

Alfa AF: 0.465 Hom.: 2101

Bravo AF: 0.452

Asia WGS AF: 0.330 AC: 1152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.20
PhyloP100		0.20
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: rs1333373; hg19: chr13-38351806; COSMIC: COSV59015941;