rs72984209

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_004621.6(TRPC6):c.2529C>T(p.Phe843Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 1,610,434 control chromosomes in the GnomAD database, including 9,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2912 hom., cov: 32)

Exomes 𝑓: 0.078 ( 6368 hom. )

Consequence

TRPC6
NM_004621.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.187

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 11-101455057-G-A is Benign according to our data. Variant chr11-101455057-G-A is described in ClinVar as [Benign]. Clinvar id is 259460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-101455057-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.187 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC6	NM_004621.6 link	c.2529C>T	p.Phe843Phe	synonymous_variant	Exon 11 of 13	ENST00000344327.8	NP_004612.2	Q9Y210-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8 link	c.2529C>T	p.Phe843Phe	synonymous_variant	Exon 11 of 13	1	NM_004621.6	ENSP00000340913.3		Q9Y210-1

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22460

AN:

151944

Hom.:

2903

Cov.:

show subpopulations

Gnomad AFR

AF:

0.350

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0903

Gnomad ASJ

AF:

0.0810

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0808

Gnomad FIN

AF:

0.0438

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.0742

Gnomad OTH

AF:

0.139

GnomAD3 exomes

AF:

0.0826

AC:

20712

AN:

250668

Hom.:

1626

AF XY:

0.0797

AC XY:

10793

AN XY:

135484

show subpopulations

Gnomad AFR exome

AF:

0.353

Gnomad AMR exome

AF:

0.0564

Gnomad ASJ exome

AF:

0.0912

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0808

Gnomad FIN exome

AF:

0.0430

Gnomad NFE exome

AF:

0.0723

Gnomad OTH exome

AF:

0.0868

GnomAD4 exome

AF:

0.0782

AC:

114024

AN:

1458372

Hom.:

6368

Cov.:

AF XY:

0.0778

AC XY:

56438

AN XY:

725578

show subpopulations

Gnomad4 AFR exome

AF:

0.365

Gnomad4 AMR exome

AF:

0.0612

Gnomad4 ASJ exome

AF:

0.0810

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.0792

Gnomad4 FIN exome

AF:

0.0438

Gnomad4 NFE exome

AF:

0.0736

Gnomad4 OTH exome

AF:

0.0892

GnomAD4 genome

AF:

0.148

AC:

22503

AN:

152062

Hom.:

2912

Cov.:

AF XY:

0.143

AC XY:

10648

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.350

Gnomad4 AMR

AF:

0.0902

Gnomad4 ASJ

AF:

0.0810

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0809

Gnomad4 FIN

AF:

0.0438

Gnomad4 NFE

AF:

0.0742

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.0952

Hom.:

653

Bravo

AF:

0.159

Asia WGS

AF:

0.0580

AC:

202

AN:

3474

EpiCase

AF:

0.0804

EpiControl

AF:

0.0841

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Focal segmental glomerulosclerosis 2

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Apr 14, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.0

DANN

Benign

0.45

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