rs4129255

chr11-101494472-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004621.6(TRPC6):c.946-2734C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,878 control chromosomes in the GnomAD database, including 14,009 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 0.42 (14009 hom., cov: 31)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC6	NM_004621.6	c.946-2734C>T		intron_variant		ENST00000344327.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC6	ENST00000344327.8	c.946-2734C>T		intron_variant		1	NM_004621.6	P1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63242 AN: 151756 Hom.: 13976 Cov.: 31

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.417 AC: 63340 AN: 151878 Hom.: 14009 Cov.: 31 AF XY: 0.413 AC XY: 30628 AN XY: 74232

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.407

Alfa AF: 0.380 Hom.: 5567

Bravo AF: 0.421

Asia WGS AF: 0.297 AC: 1035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.1
Dann	Benign	0.60

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: rs4129255; hg19: chr11-101365203;