Variant rs10501986 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004621.6(TRPC6):c.171-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,608,228 control chromosomes in the GnomAD database, including 157,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16365 hom., cov: 32)

Exomes 𝑓: 0.44 ( 140888 hom. )

Consequence

TRPC6
NM_004621.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0830

Variant links:

Genes affected

TRPC6 (HGNC:12338): (transient receptor potential cation channel subfamily C member 6) The protein encoded by this gene forms a receptor-activated calcium channel in the cell membrane. The channel is activated by diacylglycerol and is thought to be under the control of a phosphatidylinositol second messenger system. Activation of this channel occurs independently of protein kinase C and is not triggered by low levels of intracellular calcium. Defects in this gene are a cause of focal segmental glomerulosclerosis 2 (FSGS2). [provided by RefSeq, Mar 2009]

TRPC6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 11-101504818-T-C is Benign according to our data. Variant chr11-101504818-T-C is described in ClinVar as [Benign]. Clinvar id is 259456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-101504818-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC6	NM_004621.6 linkuse as main transcript	c.171-20A>G		intron_variant		ENST00000344327.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC6	ENST00000344327.8 linkuse as main transcript	c.171-20A>G		intron_variant		1	NM_004621.6	P1	Q9Y210-1

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69695

AN:

151916

Hom.:

16348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.545

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.373

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.442

GnomAD3 exomes

AF:

0.409

AC:

99636

AN:

243324

Hom.:

21418

AF XY:

0.410

AC XY:

54164

AN XY:

132066

show subpopulations

Gnomad AFR exome

AF:

0.551

Gnomad AMR exome

AF:

0.349

Gnomad ASJ exome

AF:

0.439

Gnomad EAS exome

AF:

0.180

Gnomad SAS exome

AF:

0.376

Gnomad FIN exome

AF:

0.426

Gnomad NFE exome

AF:

0.449

Gnomad OTH exome

AF:

0.421

GnomAD4 exome

AF:

0.436

AC:

634767

AN:

1456194

Hom.:

140888

Cov.:

AF XY:

0.434

AC XY:

314619

AN XY:

724200

show subpopulations

Gnomad4 AFR exome

AF:

0.559

Gnomad4 AMR exome

AF:

0.358

Gnomad4 ASJ exome

AF:

0.440

Gnomad4 EAS exome

AF:

0.214

Gnomad4 SAS exome

AF:

0.380

Gnomad4 FIN exome

AF:

0.428

Gnomad4 NFE exome

AF:

0.448

Gnomad4 OTH exome

AF:

0.432

GnomAD4 genome

AF:

0.459

AC:

69772

AN:

152034

Hom.:

16365

Cov.:

AF XY:

0.455

AC XY:

33810

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.545

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.463

Gnomad4 EAS

AF:

0.189

Gnomad4 SAS

AF:

0.375

Gnomad4 FIN

AF:

0.439

Gnomad4 NFE

AF:

0.450

Gnomad4 OTH

AF:

0.444

Alfa

AF:

0.449

Hom.:

27011

Bravo

AF:

0.460

Asia WGS

AF:

0.311

AC:

1083

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 67% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 62. Only high quality variants are reported. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Focal segmental glomerulosclerosis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Uncertain

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.45

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.45

Position offset: -1

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