rs920956

Positions:

• chr13-93451048-G-C

Variant summary

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

The NM_005708.5(GPC6):​c.161-94215G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,994 control chromosomes in the GnomAD database, including 7,429 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 0.31 (7429 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

Genes affected

GPC6 (HGNC:4454): (glypican 6) The glypicans comprise a family of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycans, and they have been implicated in the control of cell growth and cell division. The glypican encoded by this gene is a putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases. Mutations in this gene are associated with omodysplasia 1. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC6	NM_005708.5	c.161-94215G>C		intron_variant		ENST00000377047.9
GPC6	XM_047429990.1	c.-50-94215G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC6	ENST00000377047.9	c.161-94215G>C		intron_variant		1	NM_005708.5	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46960 AN: 151874 Hom.: 7424 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.309 AC: 47004 AN: 151994 Hom.: 7429 Cov.: 32 AF XY: 0.305 AC XY: 22645 AN XY: 74306

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.317

Alfa AF: 0.332 Hom.: 1057

Bravo AF: 0.302

Asia WGS AF: 0.315 AC: 1091 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.53

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: rs920956; hg19: chr13-94103301;