rs41302375

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_004621.6(TRPC6):c.-361A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 215,138 control chromosomes in the GnomAD database, including 6,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4258 hom., cov: 32)

Exomes 𝑓: 0.23 ( 1852 hom. )

Consequence

TRPC6
NM_004621.6 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.06

Publications

9 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 11-101583864-T-A is Benign according to our data. Variant chr11-101583864-T-A is described in ClinVar as Benign. ClinVar VariationId is 301926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TRPC6	NM_004621.6 link	c.-361A>T	5_prime_UTR_variant	Exon 1 of 13	ENST00000344327.8	NP_004612.2	Q9Y210-1
TRPC6	NM_001439335.1 link	c.-361A>T	5_prime_UTR_variant	Exon 1 of 11		NP_001426264.1
TRPC6	XM_047427510.1 link	c.-361A>T	5_prime_UTR_variant	Exon 1 of 11		XP_047283466.1
TRPC6	XM_047427509.1 link	c.-89+68A>T	intron_variant	Intron 1 of 12		XP_047283465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8 link	c.-361A>T		5_prime_UTR_variant	Exon 1 of 13	1	NM_004621.6	ENSP00000340913.3		Q9Y210-1
TRPC6	ENST00000526713.1 link	n.266-79066A>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34557

AN:

151848

Hom.:

4260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.519

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.245

GnomAD4 exome

AF:

0.229

AC:

14481

AN:

63172

Hom.:

1852

Cov.:

AF XY:

0.229

AC XY:

7242

AN XY:

31560

show subpopulations

African (AFR)

AF:

0.191

AC:

485

AN:

2540

American (AMR)

AF:

0.178

AC:

316

AN:

1778

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

778

AN:

2784

East Asian (EAS)

AF:

0.000414

AC:

AN:

4836

South Asian (SAS)

AF:

0.115

AC:

AN:

800

European-Finnish (FIN)

AF:

0.255

AC:

1001

AN:

3920

Middle Eastern (MID)

AF:

0.344

AC:

128

AN:

372

European-Non Finnish (NFE)

AF:

0.258

AC:

10737

AN:

41684

Other (OTH)

AF:

0.211

AC:

942

AN:

4458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

543

1086

1628

2171

2714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.227

AC:

34555

AN:

151966

Hom.:

4258

Cov.:

AF XY:

0.226

AC XY:

16815

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.202

AC:

8386

AN:

41480

American (AMR)

AF:

0.185

AC:

2822

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

967

AN:

3466

East Asian (EAS)

AF:

0.00116

AC:

AN:

5168

South Asian (SAS)

AF:

0.135

AC:

653

AN:

4820

European-Finnish (FIN)

AF:

0.276

AC:

2919

AN:

10566

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.261

AC:

17717

AN:

67884

Other (OTH)

AF:

0.242

AC:

511

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1336

2672

4008

5344

6680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

358

716

1074

1432

1790

<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:

0.232

Hom.:

552

Bravo

AF:

0.222

Asia WGS

AF:

0.0730

AC:

254

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

- -

Aug 20, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Focal segmental glomerulosclerosis 2

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

2.1

PromoterAI

0.099

Neutral

(source)

Mutation Taster

=300/0

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