11-101501510-T-C

Variant names:

• chr11-101501510-T-C
• rs10791487
• NM_004621.6:c.945+2514A>G

Variant summary

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

The NM_004621.6(TRPC6):​c.945+2514A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,810 control chromosomes in the GnomAD database, including 17,195 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 0.47 (17195 hom., cov: 30)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.784
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC6	NM_004621.6	c.945+2514A>G		intron_variant	Intron 2 of 12	ENST00000344327.8	NP_004612.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8	c.945+2514A>G		intron_variant	Intron 2 of 12	1	NM_004621.6	ENSP00000340913.3

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71139 AN: 151690 Hom.: 17177 Cov.: 30

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.469 AC: 71216 AN: 151810 Hom.: 17195 Cov.: 30 AF XY: 0.465 AC XY: 34472 AN XY: 74172

African (AFR) AF: 0.575 AC: 23811 AN: 41398

American (AMR) AF: 0.401 AC: 6114 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1615 AN: 3468

East Asian (EAS) AF: 0.187 AC: 965 AN: 5150

South Asian (SAS) AF: 0.370 AC: 1776 AN: 4796

European-Finnish (FIN) AF: 0.439 AC: 4625 AN: 10540

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30772 AN: 67910

Other (OTH) AF: 0.455 AC: 962 AN: 2112

Alfa AF: 0.331 Hom.: 851

Bravo AF: 0.471

Asia WGS AF: 0.310 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.3
DANN	Benign	0.65
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10791487; hg19: chr11-101372241;