13-94155254-G-T

Variant names:

• chr13-94155254-G-T
• rs497836
• NM_005708.5:c.877+127360G>T

Variant summary

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

The NM_005708.5(GPC6):​c.877+127360G>T 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 151,776 control chromosomes in the GnomAD database, including 27,025 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 (27025 hom., cov: 30)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.877+127360G>T		intron_variant	Intron 4 of 8	ENST00000377047.9	NP_005699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.877+127360G>T		intron_variant	Intron 4 of 8	1	NM_005708.5	ENSP00000366246.3
GPC6-AS1	ENST00000436329.2	n.485-848C>A		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88136 AN: 151658 Hom.: 27023 Cov.: 30

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.581 AC: 88156 AN: 151776 Hom.: 27025 Cov.: 30 AF XY: 0.584 AC XY: 43341 AN XY: 74162

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.585

Alfa AF: 0.630 Hom.: 12510

Bravo AF: 0.566

Asia WGS AF: 0.585 AC: 2035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.48
DANN	Benign	0.75

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: rs497836; hg19: chr13-94807508;