rs12805398

Positions:

chr11-101453039-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004621.6(TRPC6):c.2712G>A(p.Gln904Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,612 control chromosomes in the GnomAD database, including 12,329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.090 ( 842 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11487 hom. )

Consequence

TRPC6
NM_004621.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0810

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 11-101453039-C-T is Benign according to our data. Variant chr11-101453039-C-T is described in ClinVar as [Benign]. Clinvar id is 259462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-101453039-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.081 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 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.2712G>A	p.Gln904Gln	synonymous_variant	13/13	ENST00000344327.8	NP_004612.2	Q9Y210-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRPC6	ENST00000344327.8 linkuse as main transcript	c.2712G>A	p.Gln904Gln	synonymous_variant	13/13	1	NM_004621.6	ENSP00000340913.3	Q9Y210-1
TRPC6	ENST00000360497.4 linkuse as main transcript	c.2547G>A	p.Gln849Gln	synonymous_variant	12/12	1		ENSP00000353687.4	Q9Y210-3
TRPC6	ENST00000348423.8 linkuse as main transcript	c.2364G>A	p.Gln788Gln	synonymous_variant	11/11	1		ENSP00000343672.4	Q9Y210-2
TRPC6	ENST00000532133.5 linkuse as main transcript	c.2478G>A	p.Gln826Gln	synonymous_variant	12/12	5		ENSP00000435574.1	E9PJN4

Frequencies

GnomAD3 genomes

AF:

0.0901

AC:

13702

AN:

152096

Hom.:

840

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0259

Gnomad AMI

AF:

0.0910

Gnomad AMR

AF:

0.0750

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.0633

Gnomad SAS

AF:

0.0978

Gnomad FIN

AF:

0.0998

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.104

AC:

26050

AN:

251026

Hom.:

1544

AF XY:

0.109

AC XY:

14794

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.0234

Gnomad AMR exome

AF:

0.0562

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.0521

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.100

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.122

AC:

178699

AN:

1461398

Hom.:

11487

Cov.:

AF XY:

0.123

AC XY:

89468

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.0239

Gnomad4 AMR exome

AF:

0.0610

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.0900

AC:

13699

AN:

152214

Hom.:

842

Cov.:

AF XY:

0.0891

AC XY:

6631

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0260

Gnomad4 AMR

AF:

0.0749

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.0629

Gnomad4 SAS

AF:

0.0981

Gnomad4 FIN

AF:

0.0998

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.117

Hom.:

549

Bravo

AF:

0.0846

Asia WGS

AF:

0.0680

AC:

237

AN:

3478

EpiCase

AF:

0.135

EpiControl

AF:

0.133

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 25, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 12, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

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 20% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 19. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Focal segmental glomerulosclerosis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

6.1

DANN

Benign

0.55

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