chr11-101755870-T-G

Variant names:

• chr11-101755870-T-G
• rs1006330
• ENST00000526713.1:n.265+116428A>C

Variant summary

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

The ENST00000526713.1(TRPC6):​n.265+116428A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,110 control chromosomes in the GnomAD database, including 6,149 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 (6149 hom., cov: 33)
• Consequence: TRPC6 ENST00000526713.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.315 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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC6	ENST00000526713.1	TSL:3	n.265+116428A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42847 AN: 151992 Hom.: 6154 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.282 AC: 42844 AN: 152110 Hom.: 6149 Cov.: 33 AF XY: 0.282 AC XY: 21009 AN XY: 74370

African (AFR) AF: 0.222 AC: 9198 AN: 41488

American (AMR) AF: 0.315 AC: 4810 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 860 AN: 3472

East Asian (EAS) AF: 0.206 AC: 1068 AN: 5172

South Asian (SAS) AF: 0.329 AC: 1584 AN: 4820

European-Finnish (FIN) AF: 0.315 AC: 3327 AN: 10566

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21063 AN: 67998

Other (OTH) AF: 0.301 AC: 634 AN: 2108

Alfa AF: 0.294 Hom.: 1196

Bravo AF: 0.279

Asia WGS AF: 0.247 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.86
PhyloP100		0.23

Splicing

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

Other links and lift over

dbSNP: rs1006330; hg19: chr11-101626601;