11-101517985-G-A

Variant names:

• chr11-101517985-G-A
• rs10501982
• NM_004621.6:c.171-13187C>T

Variant summary

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

The NM_004621.6(TRPC6):​c.171-13187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,054 control chromosomes in the GnomAD database, including 3,509 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 0.21 (3509 hom., cov: 32)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.238 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.171-13187C>T		intron	N/A	NP_004612.2
	TRPC6	NM_001439335.1		c.171-13187C>T		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.171-13187C>T		intron	N/A	ENSP00000340913.3
	TRPC6	ENST00000360497.4	TSL:1	c.171-13187C>T		intron	N/A	ENSP00000353687.4
	TRPC6	ENST00000348423.8	TSL:1	c.171-13187C>T		intron	N/A	ENSP00000343672.4

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31920 AN: 151936 Hom.: 3510 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.210 AC: 31931 AN: 152054 Hom.: 3509 Cov.: 32 AF XY: 0.209 AC XY: 15514 AN XY: 74348

African (AFR) AF: 0.195 AC: 8070 AN: 41462

American (AMR) AF: 0.171 AC: 2619 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5186

South Asian (SAS) AF: 0.173 AC: 831 AN: 4808

European-Finnish (FIN) AF: 0.241 AC: 2548 AN: 10566

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.241 AC: 16376 AN: 67970

Other (OTH) AF: 0.199 AC: 419 AN: 2108

Alfa AF: 0.227 Hom.: 10828

Bravo AF: 0.205

Asia WGS AF: 0.0840 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.93
DANN	Benign	0.80
PhyloP100		-0.45
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: rs10501982; hg19: chr11-101388716; COSMIC: COSV60261580; COSMIC: COSV60261580;