11-101498674-C-T

Variant names:

• chr11-101498674-C-T
• rs10501980
• NM_004621.6:c.945+5350G>A

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+5350G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,010 control chromosomes in the GnomAD database, including 17,274 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 (17274 hom., cov: 31)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004621.6. 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
	TRPC6	NM_004621.6	MANE Select	c.945+5350G>A		intron	N/A	NP_004612.2
	TRPC6	NM_001439335.1		c.945+5350G>A		intron	N/A	NP_001426264.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC6	ENST00000344327.8	TSL:1 MANE Select	c.945+5350G>A		intron	N/A	ENSP00000340913.3
	TRPC6	ENST00000360497.4	TSL:1	c.945+5350G>A		intron	N/A	ENSP00000353687.4
	TRPC6	ENST00000348423.8	TSL:1	c.945+5350G>A		intron	N/A	ENSP00000343672.4

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71329 AN: 151892 Hom.: 17256 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.440

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: 0.470 AC: 71405 AN: 152010 Hom.: 17274 Cov.: 31 AF XY: 0.465 AC XY: 34592 AN XY: 74332

African (AFR) AF: 0.577 AC: 23929 AN: 41452

American (AMR) AF: 0.402 AC: 6135 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1611 AN: 3462

East Asian (EAS) AF: 0.188 AC: 967 AN: 5156

South Asian (SAS) AF: 0.368 AC: 1776 AN: 4820

European-Finnish (FIN) AF: 0.440 AC: 4648 AN: 10564

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

European-Non Finnish (NFE) AF: 0.453 AC: 30804 AN: 67974

Other (OTH) AF: 0.456 AC: 959 AN: 2104

Alfa AF: 0.464 Hom.: 2828

Bravo AF: 0.472

Asia WGS AF: 0.306 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.47
PhyloP100		-0.38
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: rs10501980; hg19: chr11-101369405;