rs145077205

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_004621.6(TRPC6):c.2142G>T(p.Thr714Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,612,764 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 51 hom. )

Consequence

TRPC6
NM_004621.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5O:1

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:

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=-0.23).

BP6

Variant 11-101472200-C-A is Benign according to our data. Variant chr11-101472200-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 236162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-101472200-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.119 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00405 (616/152208) while in subpopulation SAS AF= 0.017 (82/4824). AF 95% confidence interval is 0.014. There are 3 homozygotes in gnomad4. There are 309 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 616 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC6	NM_004621.6 linkuse as main transcript	c.2142G>T	p.Thr714Thr	synonymous_variant	8/13	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.2142G>T	p.Thr714Thr	synonymous_variant	8/13	1	NM_004621.6	ENSP00000340913.3	Q9Y210-1
TRPC6	ENST00000360497.4 linkuse as main transcript	c.1977G>T	p.Thr659Thr	synonymous_variant	7/12	1		ENSP00000353687.4	Q9Y210-3
TRPC6	ENST00000348423.8 linkuse as main transcript	c.1794G>T	p.Thr598Thr	synonymous_variant	6/11	1		ENSP00000343672.4	Q9Y210-2
TRPC6	ENST00000532133.5 linkuse as main transcript	c.1908G>T	p.Thr636Thr	synonymous_variant	7/12	5		ENSP00000435574.1	E9PJN4

Frequencies

GnomAD3 genomes

AF:

0.00407

AC:

619

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00648

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.000945

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00501

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00581

AC:

1455

AN:

250504

Hom.:

AF XY:

0.00715

AC XY:

968

AN XY:

135410

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.00646

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0189

Gnomad FIN exome

AF:

0.000883

Gnomad NFE exome

AF:

0.00555

Gnomad OTH exome

AF:

0.00557

GnomAD4 exome

AF:

0.00536

AC:

7828

AN:

1460556

Hom.:

Cov.:

AF XY:

0.00594

AC XY:

4313

AN XY:

726616

show subpopulations

Gnomad4 AFR exome

AF:

0.000688

Gnomad4 AMR exome

AF:

0.00342

Gnomad4 ASJ exome

AF:

0.00678

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0199

Gnomad4 FIN exome

AF:

0.00124

Gnomad4 NFE exome

AF:

0.00468

Gnomad4 OTH exome

AF:

0.00635

GnomAD4 genome

AF:

0.00405

AC:

616

AN:

152208

Hom.:

Cov.:

AF XY:

0.00415

AC XY:

309

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00648

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.000945

Gnomad4 NFE

AF:

0.00501

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00307

Hom.:

Bravo

AF:

0.00369

EpiCase

AF:

0.00764

EpiControl

AF:

0.00747

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Focal segmental glomerulosclerosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Sep 06, 2022

- -

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. -

Prednisolone response

Other:1

drug response, no assertion criteria provided

research

Genetic Testing Lab, Ashok and Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences

Jan 18, 2016

- sensitive to standard corticosteroid therapy

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

0.15

DANN

Benign

0.61

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