rs12275715

Positions:

• chr11-101519716-A-T

Variant summary

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

The NM_004621.6(TRPC6):​c.171-14918T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 153,996 control chromosomes in the GnomAD database, including 316 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 0.049 (314 hom., cov: 30)
  • Exomes 𝑓: 0.046 (2 hom.)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC6	NM_004621.6	c.171-14918T>A		intron_variant		ENST00000344327.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC6	ENST00000344327.8	c.171-14918T>A		intron_variant		1	NM_004621.6	P1

Frequencies

GnomAD3 genomes AF: 0.0485 AC: 7370 AN: 151908 Hom.: 311 Cov.: 30

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0527

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0292

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.0462 AC: 91 AN: 1970 Hom.: 2 AF XY: 0.0388 AC XY: 39 AN XY: 1006

Gnomad4 AFR exome AF: 0.0806

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.0294

Gnomad4 FIN exome AF: 0.0579

Gnomad4 NFE exome AF: 0.0217

Gnomad4 OTH exome AF: 0.0362

GnomAD4 genome AF: 0.0486 AC: 7387 AN: 152026 Hom.: 314 Cov.: 30 AF XY: 0.0489 AC XY: 3632 AN XY: 74312

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0268

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0223

Gnomad4 FIN AF: 0.0527

Gnomad4 NFE AF: 0.0291

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0420 Hom.: 23

Bravo AF: 0.0483

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.8
DANN	Benign	0.78

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: rs12275715; hg19: chr11-101390447;