13-93838807-A-G

Variant names:

• chr13-93838807-A-G
• rs2150127
• NM_005708.5:c.711+8262A>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.711+8262A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0736 in 152,060 control chromosomes in the GnomAD database, including 635 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 0.074 (635 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500
• Publications: 2 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-AS2 (HGNC:39910): (GPC6 antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.711+8262A>G		intron_variant	Intron 3 of 8	ENST00000377047.9	NP_005699.1
GPC6-AS2	NR_046536.1	n.153-2663T>C		intron_variant	Intron 3 of 6
GPC6	XM_017020300.2	c.501+8262A>G		intron_variant	Intron 3 of 8		XP_016875789.1
GPC6	XM_047429990.1	c.501+8262A>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.711+8262A>G		intron_variant	Intron 3 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11160 AN: 151942 Hom.: 632 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0690

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

GnomAD4 genome AF: 0.0736 AC: 11197 AN: 152060 Hom.: 635 Cov.: 32 AF XY: 0.0776 AC XY: 5762 AN XY: 74298

African (AFR) AF: 0.106 AC: 4384 AN: 41496

American (AMR) AF: 0.128 AC: 1959 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0265 AC: 92 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1158 AN: 5098

South Asian (SAS) AF: 0.174 AC: 840 AN: 4814

European-Finnish (FIN) AF: 0.0464 AC: 491 AN: 10576

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0301 AC: 2050 AN: 68024

Other (OTH) AF: 0.0706 AC: 149 AN: 2110

Alfa AF: 0.0490 Hom.: 494

Bravo AF: 0.0798

Asia WGS AF: 0.197 AC: 687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.42
PhyloP100		-0.50
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: rs2150127; hg19: chr13-94491060;