rs4326755

Positions:

• chr11-101578627-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.170+4707C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,872 control chromosomes in the GnomAD database, including 18,342 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 0.48 (18342 hom., cov: 32)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPC6	NM_004621.6	c.170+4707C>T		intron_variant		ENST00000344327.8	NP_004612.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8	c.170+4707C>T		intron_variant		1	NM_004621.6	ENSP00000340913	P1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73153 AN: 151756 Hom.: 18326 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.482 AC: 73206 AN: 151872 Hom.: 18342 Cov.: 32 AF XY: 0.483 AC XY: 35824 AN XY: 74222

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.484

Alfa AF: 0.527 Hom.: 20691

Bravo AF: 0.475

Asia WGS AF: 0.558 AC: 1933 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.29

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: rs4326755; hg19: chr11-101449358;