ENST00000527374.1:n.830+147C>T

Variant names:

• chr11-101585271-C-T
• rs3824935
• ENST00000527374.1:n.830+147C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000527374.1(ENSG00000293058):​n.830+147C>T variant causes a intron 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: ENSG00000293058 ENST00000527374.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• Publications: 5 publications found

Genes affected

ENSG00000293058 (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]

TRPC6 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000293058	ENST00000527374.1	n.830+147C>T		intron_variant	Intron 1 of 2	1
TRPC6	ENST00000526713.1	n.266-80473G>A		intron_variant	Intron 1 of 1	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0177 AC: 735 AN: 41488

American (AMR) AF: 0.0754 AC: 1152 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0932 AC: 323 AN: 3466

East Asian (EAS) AF: 0.105 AC: 544 AN: 5160

South Asian (SAS) AF: 0.0620 AC: 298 AN: 4804

European-Finnish (FIN) AF: 0.0546 AC: 576 AN: 10552

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7086 AN: 67982

Other (OTH) AF: 0.0868 AC: 183 AN: 2108

Alfa AF: 0.0937 Hom.: 388

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
PhyloP100		-0.26

Splicing

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

Other links and lift over

dbSNP: rs3824935; hg19: chr11-101456002;