rs12428018

Positions:

• chr13-94102696-C-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+74802C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,760 control chromosomes in the GnomAD database, including 9,485 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 0.34 (9485 hom., cov: 31)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.41

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC6	NM_005708.5	c.877+74802C>T		intron_variant		ENST00000377047.9	NP_005699.1
GPC6	XM_017020300.2	c.667+74802C>T		intron_variant			XP_016875789.1
GPC6	XM_047429990.1	c.667+74802C>T		intron_variant			XP_047285946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.877+74802C>T		intron_variant		1	NM_005708.5	ENSP00000366246	P1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52142 AN: 151640 Hom.: 9481 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.344 AC: 52165 AN: 151760 Hom.: 9485 Cov.: 31 AF XY: 0.343 AC XY: 25412 AN XY: 74176

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.371

Alfa AF: 0.376 Hom.: 2302

Bravo AF: 0.336

Asia WGS AF: 0.241 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.022
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: rs12428018; hg19: chr13-94754950;