11-101722330-C-T

Variant names:

• chr11-101722330-C-T
• rs10895184
• ENST00000526713.1:n.265+149968G>A

Variant summary

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

The ENST00000526713.1(TRPC6):​n.265+149968G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,088 control chromosomes in the GnomAD database, including 8,025 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 0.28 (8025 hom., cov: 32)
• Consequence: TRPC6 ENST00000526713.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• 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 = 0.79 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+149968G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42960 AN: 151970 Hom.: 8010 Cov.: 32

Gnomad AFR AF: 0.0886

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.283 AC: 42982 AN: 152088 Hom.: 8025 Cov.: 32 AF XY: 0.286 AC XY: 21258 AN XY: 74326

African (AFR) AF: 0.0885 AC: 3673 AN: 41510

American (AMR) AF: 0.381 AC: 5831 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3470

East Asian (EAS) AF: 0.810 AC: 4193 AN: 5174

South Asian (SAS) AF: 0.399 AC: 1921 AN: 4816

European-Finnish (FIN) AF: 0.306 AC: 3230 AN: 10558

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22273 AN: 67954

Other (OTH) AF: 0.314 AC: 663 AN: 2112

Alfa AF: 0.323 Hom.: 8871

Bravo AF: 0.284

Asia WGS AF: 0.558 AC: 1937 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.99
DANN	Benign	0.20
PhyloP100		0.058

Splicing

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

Other links and lift over

dbSNP: rs10895184; hg19: chr11-101593061;