rs10501987

Variant names:

• chr11-101714933-A-G
• rs10501987
• ENST00000526713.1:n.265+157365T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-101714933-A-G
• chr11-101714933-A-T

Variant summary

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

The ENST00000526713.1(TRPC6):​n.265+157365T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 152,238 control chromosomes in the GnomAD database, including 876 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 0.091 (876 hom., cov: 32)
• Consequence: TRPC6 ENST00000526713.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000526713.1	n.265+157365T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.0910 AC: 13845 AN: 152120 Hom.: 863 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0602

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0526

Gnomad OTH AF: 0.0864

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

GnomAD4 genome AF: 0.0912 AC: 13883 AN: 152238 Hom.: 876 Cov.: 32 AF XY: 0.0903 AC XY: 6718 AN XY: 74434

African (AFR) AF: 0.171 AC: 7107 AN: 41514

American (AMR) AF: 0.0625 AC: 956 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3472

East Asian (EAS) AF: 0.0604 AC: 313 AN: 5186

South Asian (SAS) AF: 0.0612 AC: 295 AN: 4822

European-Finnish (FIN) AF: 0.0759 AC: 805 AN: 10604

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0526 AC: 3577 AN: 68016

Other (OTH) AF: 0.0855 AC: 181 AN: 2116

Alfa AF: 0.0563 Hom.: 213

Bravo AF: 0.0927

Asia WGS AF: 0.0720 AC: 249 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.59
PhyloP100		-0.30

Splicing

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

Other links and lift over

dbSNP: rs10501987; hg19: chr11-101585664;