Variant 11-101504884-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_004621.6(TRPC6):c.171-86G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,473,998 control chromosomes in the GnomAD database, including 143,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16345 hom., cov: 32)

Exomes 𝑓: 0.43 ( 126987 hom. )

Consequence

TRPC6
NM_004621.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.119

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:

TRPC6 (HGNC:):

TRPC6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 11-101504884-C-G is Benign according to our data. Variant chr11-101504884-C-G is described in ClinVar as [Benign]. Clinvar id is 1261382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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	Protein	UniProt
TRPC6	NM_004621.6 linkuse as main transcript	c.171-86G>C		intron_variant		ENST00000344327.8	NP_004612.2	Q9Y210-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8 linkuse as main transcript	c.171-86G>C		intron_variant		1	NM_004621.6	ENSP00000340913.3		Q9Y210-1

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69644

AN:

151888

Hom.:

16328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.545

Gnomad AMI

AF:

0.475

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.464

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.441

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.443

GnomAD4 exome

AF:

0.435

AC:

574737

AN:

1321994

Hom.:

126987

AF XY:

0.432

AC XY:

283576

AN XY:

656090

show subpopulations

Gnomad4 AFR exome

AF:

0.556

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.429

Gnomad4 EAS exome

AF:

0.215

Gnomad4 SAS exome

AF:

0.370

Gnomad4 FIN exome

AF:

0.427

Gnomad4 NFE exome

AF:

0.448

Gnomad4 OTH exome

AF:

0.431

GnomAD4 genome

AF:

0.459

AC:

69720

AN:

152004

Hom.:

16345

Cov.:

AF XY:

0.455

AC XY:

33789

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.545

Gnomad4 AMR

AF:

0.395

Gnomad4 ASJ

AF:

0.464

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.369

Gnomad4 FIN

AF:

0.441

Gnomad4 NFE

AF:

0.450

Gnomad4 OTH

AF:

0.445

Alfa

AF:

0.255

Hom.:

451

Bravo

AF:

0.460

Asia WGS

AF:

0.307

AC:

1067

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	GeneDx	Aug 20, 2019	- -

not specified

Benign:1

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 48% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 45. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.74

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