chr11-101488380-T-G

Position:

• chr11-101488380-T-G

Variant summary

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

The NM_004621.6(TRPC6):​c.1293+557A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,280 control chromosomes in the GnomAD database, including 1,620 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 0.12 (1620 hom., cov: 33)
• Consequence: TRPC6 NM_004621.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC6	NM_004621.6	c.1293+557A>C		intron_variant		ENST00000344327.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC6	ENST00000344327.8	c.1293+557A>C		intron_variant		1	NM_004621.6	P1
TRPC6	ENST00000348423.8	c.946-5215A>C		intron_variant		1
TRPC6	ENST00000360497.4	c.1128+3176A>C		intron_variant		1
TRPC6	ENST00000532133.5	c.1293+557A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18398 AN: 152162 Hom.: 1619 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0950

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0840

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.121 AC: 18419 AN: 152280 Hom.: 1620 Cov.: 33 AF XY: 0.115 AC XY: 8563 AN XY: 74462

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.0725

Gnomad4 ASJ AF: 0.0859

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0957

Gnomad4 FIN AF: 0.0158

Gnomad4 NFE AF: 0.0840

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0819 Hom.: 304

Bravo AF: 0.130

Asia WGS AF: 0.0510 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.18
DANN	Benign	0.74

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: rs7945727; hg19: chr11-101359111;