11-101452402-A-C

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.*553T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 154,704 control chromosomes in the GnomAD database, including 10,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (10117 hom., cov: 32)
  • Exomes 𝑓: 0.14 (35 hom.)
• Consequence: TRPC6 NM_004621.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.59

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=-0.94).
• BP6: Variant 11-101452402-A-C is Benign according to our data. Variant chr11-101452402-A-C is described in ClinVar as [Benign]. Clinvar id is 301887.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC6	NM_004621.6	c.*553T>G		3_prime_UTR_variant	13/13	ENST00000344327.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC6	ENST00000344327.8	c.*553T>G		3_prime_UTR_variant	13/13	1	NM_004621.6	P1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48186 AN: 151948 Hom.: 10077 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0653

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.141 AC: 373 AN: 2638 Hom.: 35 Cov.: 0 AF XY: 0.137 AC XY: 189 AN XY: 1380

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.0161

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.318 AC: 48284 AN: 152066 Hom.: 10117 Cov.: 32 AF XY: 0.310 AC XY: 23017 AN XY: 74352

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0648

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.314

Alfa AF: 0.249 Hom.: 2649

Bravo AF: 0.331

Asia WGS AF: 0.194 AC: 674 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Focal segmental glomerulosclerosis 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.28
Dann	Benign	0.45

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: rs7931399; hg19: chr11-101323133;