rs1408219

Variant names:

• chr13-93401280-T-C
• rs1408219
• NM_005708.5:c.161-143983T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 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.161-143983T>C		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.161-143983T>C		intron	N/A	ENSP00000366246.3

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

African (AFR) AF: 0.195 AC: 8015 AN: 41124

American (AMR) AF: 0.112 AC: 1695 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 366 AN: 3468

East Asian (EAS) AF: 0.0284 AC: 144 AN: 5068

South Asian (SAS) AF: 0.116 AC: 556 AN: 4776

European-Finnish (FIN) AF: 0.139 AC: 1457 AN: 10462

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.114 AC: 7765 AN: 67878

Other (OTH) AF: 0.130 AC: 273 AN: 2096

Alfa AF: 0.120 Hom.: 659

Bravo AF: 0.133

Asia WGS AF: 0.0850 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.74
PhyloP100		-0.069
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: rs1408219; hg19: chr13-94053533;