rs920956

Variant names:

• chr13-93451048-G-C
• rs920956
• NM_005708.5:c.161-94215G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

GPC6 Gene-Disease associations (from GenCC):

• autosomal recessive omodysplasia

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.161-94215G>C		intron_variant	Intron 1 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_047429990.1	c.-50-94215G>C		intron_variant	Intron 1 of 8		XP_047285946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.161-94215G>C		intron_variant	Intron 1 of 8	1	NM_005708.5	ENSP00000366246.3

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

African (AFR) AF: 0.249 AC: 10339 AN: 41468

American (AMR) AF: 0.253 AC: 3862 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3466

East Asian (EAS) AF: 0.359 AC: 1852 AN: 5156

South Asian (SAS) AF: 0.287 AC: 1383 AN: 4822

European-Finnish (FIN) AF: 0.297 AC: 3141 AN: 10560

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.358 AC: 24304 AN: 67948

Other (OTH) AF: 0.317 AC: 668 AN: 2106

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
PhyloP100		0.048
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs920956; hg19: chr13-94103301;