rs9301921

Variant names:

• chr13-93982736-A-G
• rs9301921
• NM_005708.5:c.712-44993A>G

Variant summary

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

The NM_005708.5(GPC6):​c.712-44993A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,182 control chromosomes in the GnomAD database, including 2,002 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 0.16 (2002 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.712-44993A>G		intron_variant	Intron 3 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_017020300.2	c.502-44993A>G		intron_variant	Intron 3 of 8		XP_016875789.1
GPC6	XM_047429990.1	c.502-44993A>G		intron_variant	Intron 3 of 8		XP_047285946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.712-44993A>G		intron_variant	Intron 3 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23742 AN: 152064 Hom.: 1999 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.156 AC: 23756 AN: 152182 Hom.: 2002 Cov.: 32 AF XY: 0.156 AC XY: 11641 AN XY: 74388

Gnomad4 AFR AF: 0.119 AC: 0.119332 AN: 0.119332

Gnomad4 AMR AF: 0.180 AC: 0.180296 AN: 0.180296

Gnomad4 ASJ AF: 0.207 AC: 0.207205 AN: 0.207205

Gnomad4 EAS AF: 0.266 AC: 0.265607 AN: 0.265607

Gnomad4 SAS AF: 0.102 AC: 0.101867 AN: 0.101867

Gnomad4 FIN AF: 0.183 AC: 0.182754 AN: 0.182754

Gnomad4 NFE AF: 0.163 AC: 0.162936 AN: 0.162936

Gnomad4 OTH AF: 0.154 AC: 0.154028 AN: 0.154028

Alfa AF: 0.161 Hom.: 1491

Bravo AF: 0.159

Asia WGS AF: 0.200 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.42
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

Publications

LitVar

Other links and lift over

dbSNP: rs9301921; hg19: chr13-94634989;