rs17096918

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004621.6(TRPC6):c.170+70G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,515,402 control chromosomes in the GnomAD database, including 12,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 1297 hom., cov: 32)

Exomes 𝑓: 0.10 ( 10829 hom. )

Consequence

TRPC6
NM_004621.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.19

Publications

7 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 11-101583264-C-T is Benign according to our data. Variant chr11-101583264-C-T is described in ClinVar as Benign. ClinVar VariationId is 1231692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC6	NM_004621.6 link	c.170+70G>A		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.170+70G>A		intron_variant	Intron 1 of 12	1	NM_004621.6	ENSP00000340913.3		Q9Y210-1

Frequencies

GnomAD3 genomes

AF:

0.0936

AC:

14234

AN:

152066

Hom.:

1289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0220

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.0867

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0785

Gnomad OTH

AF:

0.0963

GnomAD4 exome

AF:

0.101

AC:

137218

AN:

1363218

Hom.:

10829

Cov.:

AF XY:

0.104

AC XY:

69655

AN XY:

669208

show subpopulations

African (AFR)

AF:

0.0185

AC:

569

AN:

30750

American (AMR)

AF:

0.210

AC:

7315

AN:

34852

Ashkenazi Jewish (ASJ)

AF:

0.0831

AC:

1994

AN:

24000

East Asian (EAS)

AF:

0.438

AC:

15412

AN:

35156

South Asian (SAS)

AF:

0.245

AC:

18632

AN:

76022

European-Finnish (FIN)

AF:

0.122

AC:

4306

AN:

35308

Middle Eastern (MID)

AF:

0.0726

AC:

381

AN:

5246

European-Non Finnish (NFE)

AF:

0.0772

AC:

82180

AN:

1065046

Other (OTH)

AF:

0.113

AC:

6429

AN:

56838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

6751

13502

20254

27005

33756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3392

6784

10176

13568

16960

<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:

0.0937

AC:

14253

AN:

152184

Hom.:

1297

Cov.:

AF XY:

0.102

AC XY:

7603

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0220

AC:

913

AN:

41568

American (AMR)

AF:

0.156

AC:

2383

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0867

AC:

301

AN:

3472

East Asian (EAS)

AF:

0.463

AC:

2361

AN:

5100

South Asian (SAS)

AF:

0.272

AC:

1311

AN:

4822

European-Finnish (FIN)

AF:

0.133

AC:

1406

AN:

10602

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0785

AC:

5338

AN:

68000

Other (OTH)

AF:

0.101

AC:

213

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

609

1218

1828

2437

3046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.0837

Hom.:

Bravo

AF:

0.0929

Asia WGS

AF:

0.360

AC:

1249

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

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 25% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 23. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.0

(source)

DANN

Benign

0.93

PhyloP100

1.2

PromoterAI

-0.088

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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