13-94155411-C-G

Position:

• chr13-94155411-C-G

Variant summary

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

The NM_005708.5(GPC6):​c.877+127517C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,062 control chromosomes in the GnomAD database, including 6,462 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 0.28 (6462 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

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-AS1 (HGNC:39909): (GPC6 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC6	NM_005708.5	c.877+127517C>G		intron_variant		ENST00000377047.9
GPC6-AS1	NR_046535.1	n.485-1005G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC6	ENST00000377047.9	c.877+127517C>G		intron_variant		1	NM_005708.5	P1
GPC6-AS1	ENST00000436329.2	n.485-1005G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42465 AN: 151944 Hom.: 6446 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.280 AC: 42524 AN: 152062 Hom.: 6462 Cov.: 32 AF XY: 0.279 AC XY: 20721 AN XY: 74332

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.270

Alfa AF: 0.127 Hom.: 206

Bravo AF: 0.290

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.7
DANN	Benign	0.73

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: rs1328822; hg19: chr13-94807665;