rs7105083

Positions:

• chr11-101455239-G-A

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.2485-138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 696,594 control chromosomes in the GnomAD database, including 24,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (9617 hom., cov: 32)
  • Exomes 𝑓: 0.22 (15307 hom.)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.50

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=-0.99).
• BP6: Variant 11-101455239-G-A is Benign according to our data. Variant chr11-101455239-G-A is described in ClinVar as [Benign]. Clinvar id is 1234385.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC6	NM_004621.6	c.2485-138C>T		intron_variant		ENST00000344327.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC6	ENST00000344327.8	c.2485-138C>T		intron_variant		1	NM_004621.6	P1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47310 AN: 151936 Hom.: 9584 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0663

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.224 AC: 121871 AN: 544540 Hom.: 15307 Cov.: 7 AF XY: 0.224 AC XY: 65111 AN XY: 290696

Gnomad4 AFR exome AF: 0.584

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.223

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.312 AC: 47399 AN: 152054 Hom.: 9617 Cov.: 32 AF XY: 0.304 AC XY: 22583 AN XY: 74326

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0658

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.308

Alfa AF: 0.275 Hom.: 922

Bravo AF: 0.324

Asia WGS AF: 0.189 AC: 658 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

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.010
DANN	Benign	0.18

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: rs7105083; hg19: chr11-101325970;