chr11-101472227-G-A

Position:

chr11-101472227-G-A

Variant summary

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

The NM_004621.6(TRPC6):c.2115C>T(p.Tyr705=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 1,612,978 control chromosomes in the GnomAD database, including 727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 248 hom., cov: 32)

Exomes 𝑓: 0.022 ( 479 hom. )

Consequence

TRPC6
NM_004621.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.453

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 11-101472227-G-A is Benign according to our data. Variant chr11-101472227-G-A is described in ClinVar as [Benign]. Clinvar id is 259458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-101472227-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.453 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0997 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.2115C>T	p.Tyr705=	synonymous_variant	8/13	ENST00000344327.8	NP_004612.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8 linkuse as main transcript	c.2115C>T	p.Tyr705=	synonymous_variant	8/13	1	NM_004621.6	ENSP00000340913	P1	Q9Y210-1
TRPC6	ENST00000360497.4 linkuse as main transcript	c.1950C>T	p.Tyr650=	synonymous_variant	7/12	1		ENSP00000353687		Q9Y210-3
TRPC6	ENST00000348423.8 linkuse as main transcript	c.1767C>T	p.Tyr589=	synonymous_variant	6/11	1		ENSP00000343672		Q9Y210-2
TRPC6	ENST00000532133.5 linkuse as main transcript	c.1881C>T	p.Tyr627=	synonymous_variant	7/12	5		ENSP00000435574

Frequencies

GnomAD3 genomes

AF:

0.0411

AC:

6245

AN:

152062

Hom.:

248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0183

Gnomad ASJ

AF:

0.0265

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00624

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0218

Gnomad OTH

AF:

0.0296

GnomAD3 exomes

AF:

0.0200

AC:

4996

AN:

250108

Hom.:

140

AF XY:

0.0182

AC XY:

2458

AN XY:

135220

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.00988

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00649

Gnomad FIN exome

AF:

0.00755

Gnomad NFE exome

AF:

0.0196

Gnomad OTH exome

AF:

0.0219

GnomAD4 exome

AF:

0.0216

AC:

31622

AN:

1460798

Hom.:

479

Cov.:

AF XY:

0.0208

AC XY:

15110

AN XY:

726706

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.0247

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00695

Gnomad4 FIN exome

AF:

0.00852

Gnomad4 NFE exome

AF:

0.0217

Gnomad4 OTH exome

AF:

0.0252

GnomAD4 genome

AF:

0.0411

AC:

6258

AN:

152180

Hom.:

248

Cov.:

AF XY:

0.0388

AC XY:

2886

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0183

Gnomad4 ASJ

AF:

0.0265

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00580

Gnomad4 FIN

AF:

0.00624

Gnomad4 NFE

AF:

0.0218

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.0312

Hom.:

Bravo

AF:

0.0444

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.0198

EpiControl

AF:

0.0191

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 12, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Focal segmental glomerulosclerosis 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 15, 2017	- -
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. -

Focal segmental glomerulosclerosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Oct 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.4

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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