rs9284274

chr13-93827664-A-G

Variant summary

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

The NM_005708.5(GPC6):c.320-2490A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,060 control chromosomes in the GnomAD database, including 14,808 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 0.42 (14808 hom., cov: 33)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC6	NM_005708.5	c.320-2490A>G		intron_variant		ENST00000377047.9
GPC6-AS2	NR_046536.1	n.380+3152T>C		intron_variant, non_coding_transcript_variant
GPC6	XM_017020300.2	c.110-2490A>G		intron_variant
GPC6	XM_047429990.1	c.110-2490A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC6	ENST00000377047.9	c.320-2490A>G		intron_variant		1	NM_005708.5	P1
GPC6-AS2	ENST00000445540.1	n.228+3152T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64170 AN: 151942 Hom.: 14762 Cov.: 33

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.423 AC: 64265 AN: 152060 Hom.: 14808 Cov.: 33 AF XY: 0.424 AC XY: 31548 AN XY: 74332

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.420

Alfa AF: 0.379 Hom.: 1441

Bravo AF: 0.439

Asia WGS AF: 0.470 AC: 1631 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.56
Dann	Benign	0.45

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: rs9284274; hg19: chr13-94479917;