11-101534487-A-G

Variant names:

• chr11-101534487-A-G
• rs7931676
• NM_004621.6:c.171-29689T>C

Variant summary

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

The NM_004621.6(TRPC6):​c.171-29689T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 151,984 control chromosomes in the GnomAD database, including 4,770 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 0.22 (4770 hom., cov: 31)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC6	NM_004621.6	c.171-29689T>C		intron_variant	Intron 1 of 12	ENST00000344327.8	NP_004612.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8	c.171-29689T>C		intron_variant	Intron 1 of 12	1	NM_004621.6	ENSP00000340913.3

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33416 AN: 151866 Hom.: 4766 Cov.: 31

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.00502

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.220 AC: 33418 AN: 151984 Hom.: 4770 Cov.: 31 AF XY: 0.215 AC XY: 15992 AN XY: 74274

African (AFR) AF: 0.0699 AC: 2898 AN: 41466

American (AMR) AF: 0.208 AC: 3174 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1037 AN: 3466

East Asian (EAS) AF: 0.00503 AC: 26 AN: 5170

South Asian (SAS) AF: 0.239 AC: 1153 AN: 4820

European-Finnish (FIN) AF: 0.257 AC: 2714 AN: 10560

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.318 AC: 21610 AN: 67924

Other (OTH) AF: 0.217 AC: 457 AN: 2108

Alfa AF: 0.277 Hom.: 3208

Bravo AF: 0.210

Asia WGS AF: 0.101 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.32
DANN	Benign	0.70
PhyloP100		-0.97
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: rs7931676; hg19: chr11-101405218;