rs17096918

chr11-101583264-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 1.19

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1231692.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC6	NM_004621.6	c.170+70G>A		intron_variant		ENST00000344327.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC6	ENST00000344327.8	c.170+70G>A		intron_variant		1	NM_004621.6	P1

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

Gnomad4 AFR exome AF: 0.0185

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.0831

Gnomad4 EAS exome AF: 0.438

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.0772

Gnomad4 OTH exome AF: 0.113

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

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.0785

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0858 Hom.: 84

Bravo AF: 0.0929

Asia WGS AF: 0.360 AC: 1249 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	9.0
Dann	Benign	0.93

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

Publications

LitVar

Other links and lift over

dbSNP: rs17096918; hg19: chr11-101453995; COSMIC: COSV60262978; COSMIC: COSV60262978;