chr13-94218511-G-A

Variant names:

• chr13-94218511-G-A
• rs1572050
• NM_005708.5:c.878-67838G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005708.5(GPC6):​c.878-67838G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,052 control chromosomes in the GnomAD database, including 2,088 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 0.14 (2088 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive omodysplasia

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005708.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC6	NM_005708.5	MANE Select	c.878-67838G>A		intron	N/A	NP_005699.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC6	ENST00000377047.9	TSL:1 MANE Select	c.878-67838G>A		intron	N/A	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21875 AN: 151934 Hom.: 2073 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0707

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0863

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.144 AC: 21932 AN: 152052 Hom.: 2088 Cov.: 32 AF XY: 0.142 AC XY: 10580 AN XY: 74326

African (AFR) AF: 0.251 AC: 10387 AN: 41430

American (AMR) AF: 0.147 AC: 2249 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 474 AN: 3470

East Asian (EAS) AF: 0.189 AC: 977 AN: 5170

South Asian (SAS) AF: 0.168 AC: 807 AN: 4816

European-Finnish (FIN) AF: 0.0707 AC: 749 AN: 10590

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0863 AC: 5870 AN: 67982

Other (OTH) AF: 0.136 AC: 288 AN: 2112

Alfa AF: 0.106 Hom.: 3237

Bravo AF: 0.155

Asia WGS AF: 0.171 AC: 593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.58
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1572050; hg19: chr13-94870765;