Variant chr13-37636909-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016179.4(TRPC4):c.2928A>G(p.Arg976=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00528 in 1,609,486 control chromosomes in the GnomAD database, including 392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 193 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 199 hom. )

Consequence

TRPC4
NM_016179.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0910

Variant links:

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]

TRPC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 13-37636909-T-C is Benign according to our data. Variant chr13-37636909-T-C is described in ClinVar as [Benign]. Clinvar id is 778695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.091 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC4	NM_016179.4 linkuse as main transcript	c.2928A>G	p.Arg976=	synonymous_variant	11/11	ENST00000379705.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC4	ENST00000379705.8 linkuse as main transcript	c.2928A>G	p.Arg976=	synonymous_variant	11/11	1	NM_016179.4	P4	Q9UBN4-1

Frequencies

GnomAD3 genomes

AF:

0.0280

AC:

4263

AN:

152086

Hom.:

191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.00766

AC:

1901

AN:

248032

Hom.:

AF XY:

0.00544

AC XY:

728

AN XY:

133936

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.00560

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.000199

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000348

Gnomad OTH exome

AF:

0.00531

GnomAD4 exome

AF:

0.00290

AC:

4232

AN:

1457282

Hom.:

199

Cov.:

AF XY:

0.00250

AC XY:

1814

AN XY:

724566

show subpopulations

Gnomad4 AFR exome

AF:

0.0980

Gnomad4 AMR exome

AF:

0.00705

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000233

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000123

Gnomad4 OTH exome

AF:

0.00741

GnomAD4 genome

AF:

0.0281

AC:

4271

AN:

152204

Hom.:

193

Cov.:

AF XY:

0.0277

AC XY:

2063

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0965

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.00782

Hom.:

Bravo

AF:

0.0330

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.69

DANN

Benign

0.52

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over