rs17096918

Variant names:

• chr11-101583264-C-T
• rs17096918
• NM_004621.6:c.170+70G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004621.6(TRPC6):​c.170+70G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,515,402 control chromosomes in the GnomAD database, including 12,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (1297 hom., cov: 32)
  • Exomes 𝑓: 0.10 (10829 hom.)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.19
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 11-101583264-C-T is Benign according to our data. Variant chr11-101583264-C-T is described in ClinVar as Benign. ClinVar VariationId is 1231692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 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.170+70G>A		intron	N/A	NP_004612.2
	TRPC6	NM_001439335.1		c.170+70G>A		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.170+70G>A		intron	N/A	ENSP00000340913.3
	TRPC6	ENST00000360497.4	TSL:1	c.170+70G>A		intron	N/A	ENSP00000353687.4
	TRPC6	ENST00000348423.8	TSL:1	c.170+70G>A		intron	N/A	ENSP00000343672.4

Frequencies

GnomAD3 genomes AF: 0.0936 AC: 14234 AN: 152066 Hom.: 1289 Cov.: 32

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0785

Gnomad OTH AF: 0.0963

GnomAD4 exome AF: 0.101 AC: 137218 AN: 1363218 Hom.: 10829 Cov.: 31 AF XY: 0.104 AC XY: 69655 AN XY: 669208

African (AFR) AF: 0.0185 AC: 569 AN: 30750

American (AMR) AF: 0.210 AC: 7315 AN: 34852

Ashkenazi Jewish (ASJ) AF: 0.0831 AC: 1994 AN: 24000

East Asian (EAS) AF: 0.438 AC: 15412 AN: 35156

South Asian (SAS) AF: 0.245 AC: 18632 AN: 76022

European-Finnish (FIN) AF: 0.122 AC: 4306 AN: 35308

Middle Eastern (MID) AF: 0.0726 AC: 381 AN: 5246

European-Non Finnish (NFE) AF: 0.0772 AC: 82180 AN: 1065046

Other (OTH) AF: 0.113 AC: 6429 AN: 56838

GnomAD4 genome AF: 0.0937 AC: 14253 AN: 152184 Hom.: 1297 Cov.: 32 AF XY: 0.102 AC XY: 7603 AN XY: 74384

African (AFR) AF: 0.0220 AC: 913 AN: 41568

American (AMR) AF: 0.156 AC: 2383 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 301 AN: 3472

East Asian (EAS) AF: 0.463 AC: 2361 AN: 5100

South Asian (SAS) AF: 0.272 AC: 1311 AN: 4822

European-Finnish (FIN) AF: 0.133 AC: 1406 AN: 10602

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0785 AC: 5338 AN: 68000

Other (OTH) AF: 0.101 AC: 213 AN: 2110

Alfa AF: 0.0837 Hom.: 84

Bravo AF: 0.0929

Asia WGS AF: 0.360 AC: 1249 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.0
DANN	Benign	0.93
PhyloP100		1.2
PromoterAI		-0.088	Neutral
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: rs17096918; hg19: chr11-101453995; COSMIC: COSV60262978; COSMIC: COSV60262978;