rs1006330

chr11-101755870-T-G

Variant summary

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

The ENST00000526713.1(TRPC6):n.265+116428A>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,110 control chromosomes in the GnomAD database, including 6,149 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 0.28 (6149 hom., cov: 33)
• Consequence: TRPC6 ENST00000526713.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC6	ENST00000526713.1	n.265+116428A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42847 AN: 151992 Hom.: 6154 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.282 AC: 42844 AN: 152110 Hom.: 6149 Cov.: 33 AF XY: 0.282 AC XY: 21009 AN XY: 74370

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.301

Alfa AF: 0.297 Hom.: 1180

Bravo AF: 0.279

Asia WGS AF: 0.247 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	10
Dann	Benign	0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1006330; hg19: chr11-101626601;