chr11-101488380-T-G

Variant names:

• chr11-101488380-T-G
• rs7945727
• NM_004621.6:c.1293+557A>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.1293+557A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,280 control chromosomes in the GnomAD database, including 1,620 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 0.12 (1620 hom., cov: 33)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC6	NM_004621.6	MANE Select	c.1293+557A>C		intron	N/A	NP_004612.2
	TRPC6	NM_001439335.1		c.946-5215A>C		intron	N/A	NP_001426264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC6	ENST00000344327.8	TSL:1 MANE Select	c.1293+557A>C		intron	N/A	ENSP00000340913.3	Q9Y210-1
	TRPC6	ENST00000360497.4	TSL:1	c.1128+3176A>C		intron	N/A	ENSP00000353687.4	Q9Y210-3
	TRPC6	ENST00000348423.8	TSL:1	c.946-5215A>C		intron	N/A	ENSP00000343672.4	Q9Y210-2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18398 AN: 152162 Hom.: 1619 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0950

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0840

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.121 AC: 18419 AN: 152280 Hom.: 1620 Cov.: 33 AF XY: 0.115 AC XY: 8563 AN XY: 74462

African (AFR) AF: 0.249 AC: 10327 AN: 41532

American (AMR) AF: 0.0725 AC: 1110 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0859 AC: 298 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0957 AC: 462 AN: 4830

European-Finnish (FIN) AF: 0.0158 AC: 168 AN: 10626

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0840 AC: 5715 AN: 68012

Other (OTH) AF: 0.113 AC: 239 AN: 2116

Alfa AF: 0.0845 Hom.: 368

Bravo AF: 0.130

Asia WGS AF: 0.0510 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.18
DANN	Benign	0.74
PhyloP100		-1.2
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: rs7945727; hg19: chr11-101359111;