rs947992

Variant names:

• chr11-101614310-T-A
• rs947992
• ENST00000526713.1:n.266-109512A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-101614310-T-A
• chr11-101614310-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000526713.1(TRPC6):​n.266-109512A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,232 control chromosomes in the GnomAD database, including 51,554 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (51554 hom., cov: 33)
• Consequence: TRPC6 ENST00000526713.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000526713.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC6	ENST00000526713.1	TSL:3	n.266-109512A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124269 AN: 152114 Hom.: 51482 Cov.: 33

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.794

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.817 AC: 124400 AN: 152232 Hom.: 51554 Cov.: 33 AF XY: 0.817 AC XY: 60825 AN XY: 74410

African (AFR) AF: 0.939 AC: 39035 AN: 41558

American (AMR) AF: 0.836 AC: 12788 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2550 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5176 AN: 5182

South Asian (SAS) AF: 0.877 AC: 4234 AN: 4826

European-Finnish (FIN) AF: 0.724 AC: 7663 AN: 10582

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.744 AC: 50587 AN: 68004

Other (OTH) AF: 0.797 AC: 1687 AN: 2116

Alfa AF: 0.701 Hom.: 2050

Bravo AF: 0.830

Asia WGS AF: 0.941 AC: 3272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.28
DANN	Benign	0.40
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs947992; hg19: chr11-101485041;