rs10501986

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004621.6(TRPC6):c.171-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,608,228 control chromosomes in the GnomAD database, including 157,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16365 hom., cov: 32)

Exomes 𝑓: 0.44 ( 140888 hom. )

Consequence

TRPC6
NM_004621.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0830

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

focal segmental glomerulosclerosis 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TRPC6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 11-101504818-T-C is Benign according to our data. Variant chr11-101504818-T-C is described in ClinVar as Benign. ClinVar VariationId is 259456.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 rank	MANE	Protein	UniProt
TRPC6	NM_004621.6 link	c.171-20A>G		intron_variant	Intron 1 of 12	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.171-20A>G		intron_variant	Intron 1 of 12	1	NM_004621.6	ENSP00000340913.3		Q9Y210-1

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69695

AN:

151916

Hom.:

16348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.545

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.373

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.442

GnomAD2 exomes

AF:

0.409

AC:

99636

AN:

243324

AF XY:

0.410

show subpopulations

Gnomad AFR exome

AF:

0.551

Gnomad AMR exome

AF:

0.349

Gnomad ASJ exome

AF:

0.439

Gnomad EAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.426

Gnomad NFE exome

AF:

0.449

Gnomad OTH exome

AF:

0.421

GnomAD4 exome

AF:

0.436

AC:

634767

AN:

1456194

Hom.:

140888

Cov.:

AF XY:

0.434

AC XY:

314619

AN XY:

724200

show subpopulations

African (AFR)

AF:

0.559

AC:

18541

AN:

33192

American (AMR)

AF:

0.358

AC:

15592

AN:

43564

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

11315

AN:

25708

East Asian (EAS)

AF:

0.214

AC:

8484

AN:

39662

South Asian (SAS)

AF:

0.380

AC:

32539

AN:

85552

European-Finnish (FIN)

AF:

0.428

AC:

22741

AN:

53190

Middle Eastern (MID)

AF:

0.466

AC:

2652

AN:

5690

European-Non Finnish (NFE)

AF:

0.448

AC:

496903

AN:

1109504

Other (OTH)

AF:

0.432

AC:

26000

AN:

60132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

18150

36301

54451

72602

90752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14926

29852

44778

59704

74630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.459

AC:

69772

AN:

152034

Hom.:

16365

Cov.:

AF XY:

0.455

AC XY:

33810

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.545

AC:

22608

AN:

41462

American (AMR)

AF:

0.396

AC:

6046

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.463

AC:

1606

AN:

3466

East Asian (EAS)

AF:

0.189

AC:

977

AN:

5174

South Asian (SAS)

AF:

0.375

AC:

1805

AN:

4818

European-Finnish (FIN)

AF:

0.439

AC:

4642

AN:

10566

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.450

AC:

30577

AN:

67954

Other (OTH)

AF:

0.444

AC:

936

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1946

3892

5838

7784

9730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.451

Hom.:

60313

Bravo

AF:

0.460

Asia WGS

AF:

0.311

AC:

1083

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 20, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

not specified

Benign:2

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 67% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 62. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Focal segmental glomerulosclerosis 2

Benign:1

Sep 10, 2021

Genome-Nilou Lab

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

-0.71

CADD

Uncertain

(source)

DANN

Benign

0.76

PhyloP100

-0.083

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.45

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.45

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over