rs4523817

chr13-93620709-G-C

Variant summary

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

The NM_005708.5(GPC6):c.319+75288G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,902 control chromosomes in the GnomAD database, including 8,879 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 (8879 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC6	NM_005708.5	c.319+75288G>C		intron_variant		ENST00000377047.9
GPC6	XM_017020300.2	c.109+75288G>C		intron_variant
GPC6	XM_047429990.1	c.109+75288G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC6	ENST00000377047.9	c.319+75288G>C		intron_variant		1	NM_005708.5	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51258 AN: 151784 Hom.: 8873 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.338 AC: 51287 AN: 151902 Hom.: 8879 Cov.: 32 AF XY: 0.337 AC XY: 24985 AN XY: 74232

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.350

Alfa AF: 0.361 Hom.: 1257

Bravo AF: 0.327

Asia WGS AF: 0.284 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.0
Dann	Benign	0.44

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: rs4523817; hg19: chr13-94272962;