rs3824935

chr11-101585271-C-T

Variant summary

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

The ENST00000527374.1(ENSG00000293058):n.830+147C>T 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 0.0721 in 152,050 control chromosomes in the GnomAD database, including 525 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 0.072 (525 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENST00000527374.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258

Genes affected

(HGNC:):

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 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
	ENST00000527374.1	n.830+147C>T		intron_variant, non_coding_transcript_variant		1
TRPC6	ENST00000526713.1	n.266-80473G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0722 AC: 10964 AN: 151932 Hom.: 526 Cov.: 32

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0754

Gnomad ASJ AF: 0.0932

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0620

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0882

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0721 AC: 10959 AN: 152050 Hom.: 525 Cov.: 32 AF XY: 0.0695 AC XY: 5169 AN XY: 74326

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.0754

Gnomad4 ASJ AF: 0.0932

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0620

Gnomad4 FIN AF: 0.0546

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0868

Alfa AF: 0.0937 Hom.: 341

Bravo AF: 0.0704

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.2
Dann	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3824935; hg19: chr11-101456002;