Variant rs41302375 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

TRPC6 (HGNC:):

TRPC6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
TRPC6	NM_004621.6 linkuse as main transcript	c.-361A>T	5_prime_UTR_variant	1/13	ENST00000344327.8	NP_004612.2	Q9Y210-1
TRPC6	XM_047427510.1 linkuse as main transcript	c.-361A>T	5_prime_UTR_variant	1/11		XP_047283466.1
TRPC6	XM_017018221.3 linkuse as main transcript	c.-361A>T	5_prime_UTR_variant	1/11		XP_016873710.1	Q9Y210-2
TRPC6	XM_047427509.1 linkuse as main transcript	c.-89+68A>T	intron_variant			XP_047283465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8 linkuse as main transcript	c.-361A>T		5_prime_UTR_variant	1/13	1	NM_004621.6	ENSP00000340913.3		Q9Y210-1
TRPC6	ENST00000526713.1 linkuse as main transcript	n.266-79066A>T		intron_variant		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

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.279

Gnomad4 EAS exome

AF:

0.000414

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.255

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.211

GnomAD4 genome

AF:

0.227

AC:

34555

AN:

151966

Hom.:

4258

Cov.:

AF XY:

0.226

AC XY:

16815

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.185

Gnomad4 ASJ

AF:

0.279

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.135

Gnomad4 FIN

AF:

0.276

Gnomad4 NFE

AF:

0.261

Gnomad4 OTH

AF:

0.242

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.95

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