rs1408219

chr13-93401280-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.161-143983T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,248 control chromosomes in the GnomAD database, including 1,558 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 0.13 (1558 hom., cov: 29)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC6	NM_005708.5	c.161-143983T>C		intron_variant		ENST00000377047.9
GPC6	XM_047429990.1	c.-50-143983T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC6	ENST00000377047.9	c.161-143983T>C		intron_variant		1	NM_005708.5	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20302 AN: 151128 Hom.: 1551 Cov.: 29

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.134 AC: 20339 AN: 151248 Hom.: 1558 Cov.: 29 AF XY: 0.136 AC XY: 10029 AN XY: 73894

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0284

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.130

Alfa AF: 0.119 Hom.: 593

Bravo AF: 0.133

Asia WGS AF: 0.0850 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.2
Dann	Benign	0.74

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: rs1408219; hg19: chr13-94053533;