Variant rs4542378 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004621.6(TRPC6):c.945+129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,145,114 control chromosomes in the GnomAD database, including 110,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16385 hom., cov: 32)

Exomes 𝑓: 0.43 ( 93815 hom. )

Consequence

TRPC6
NM_004621.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0700

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 11-101503895-G-A is Benign according to our data. Variant chr11-101503895-G-A is described in ClinVar as [Benign]. Clinvar id is 1231268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC6	NM_004621.6 link	c.945+129C>T		intron_variant		ENST00000344327.8	NP_004612.2	Q9Y210-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8 link	c.945+129C>T		intron_variant		1	NM_004621.6	ENSP00000340913.3		Q9Y210-1

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69709

AN:

151944

Hom.:

16368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.546

Gnomad AMI

AF:

0.475

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.464

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.444

GnomAD4 exome

AF:

0.429

AC:

426502

AN:

993052

Hom.:

93815

AF XY:

0.428

AC XY:

217504

AN XY:

507658

show subpopulations

Gnomad4 AFR exome

AF:

0.557

Gnomad4 AMR exome

AF:

0.363

Gnomad4 ASJ exome

AF:

0.443

Gnomad4 EAS exome

AF:

0.213

Gnomad4 SAS exome

AF:

0.378

Gnomad4 FIN exome

AF:

0.430

Gnomad4 NFE exome

AF:

0.445

Gnomad4 OTH exome

AF:

0.431

GnomAD4 genome

AF:

0.459

AC:

69787

AN:

152062

Hom.:

16385

Cov.:

AF XY:

0.455

AC XY:

33820

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.546

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.464

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.371

Gnomad4 FIN

AF:

0.439

Gnomad4 NFE

AF:

0.450

Gnomad4 OTH

AF:

0.446

Alfa

AF:

0.448

Hom.:

2540

Bravo

AF:

0.460

Asia WGS

AF:

0.309

AC:

1076

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.4

DANN

Benign

0.67

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