rs9524111

Variant names:

• chr13-93517648-G-A
• rs9524111
• NM_005708.5:c.161-27615G>A

Variant summary

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

The NM_005708.5(GPC6):​c.161-27615G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 151,824 control chromosomes in the GnomAD database, including 1,639 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 0.14 (1639 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.33
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.161-27615G>A		intron_variant	Intron 1 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_017020300.2	c.-51+9901G>A		intron_variant	Intron 1 of 8		XP_016875789.1
GPC6	XM_047429990.1	c.-50-27615G>A		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.161-27615G>A		intron_variant	Intron 1 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21248 AN: 151706 Hom.: 1642 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.140 AC: 21235 AN: 151824 Hom.: 1639 Cov.: 32 AF XY: 0.142 AC XY: 10508 AN XY: 74186

African (AFR) AF: 0.148 AC: 6135 AN: 41430

American (AMR) AF: 0.197 AC: 2994 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3468

East Asian (EAS) AF: 0.293 AC: 1506 AN: 5136

South Asian (SAS) AF: 0.134 AC: 648 AN: 4826

European-Finnish (FIN) AF: 0.139 AC: 1465 AN: 10536

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7644 AN: 67922

Other (OTH) AF: 0.149 AC: 315 AN: 2112

Alfa AF: 0.136 Hom.: 301

Bravo AF: 0.149

Asia WGS AF: 0.183 AC: 633 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.012
DANN	Benign	0.28
PhyloP100		-4.3
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: rs9524111; hg19: chr13-94169901;