13-94155102-T-C

Variant summary

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

The NM_005708.5(GPC6):c.877+127208T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,810 control chromosomes in the GnomAD database, including 27,064 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 0.58 (27064 hom., cov: 30)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC6	NM_005708.5	c.877+127208T>C		intron_variant		ENST00000377047.9
GPC6-AS1	NR_046535.1	n.485-696A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC6	ENST00000377047.9	c.877+127208T>C		intron_variant		1	NM_005708.5	P1
GPC6-AS1	ENST00000436329.2	n.485-696A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88194 AN: 151692 Hom.: 27062 Cov.: 30

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.581 AC: 88214 AN: 151810 Hom.: 27064 Cov.: 30 AF XY: 0.585 AC XY: 43343 AN XY: 74148

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.726

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.586

Alfa AF: 0.653 Hom.: 66320

Bravo AF: 0.567

Asia WGS AF: 0.588 AC: 2044 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	1.7
Dann	Benign	0.42

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: rs589258; hg19: chr13-94807356;