rs17702471

Variant names:

• chr13-93224864-A-G
• rs17702471
• XM_047429990.1:c.-1869A>G

Variant summary

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

The XM_047429990.1(GPC6):​c.-1869A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,174 control chromosomes in the GnomAD database, including 2,328 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 0.16 (2328 hom., cov: 33)
• Consequence: GPC6 XM_047429990.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 6 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

ENSG00000302670 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000788637.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000302670	ENST00000788637.1		n.370+4482A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24713 AN: 152056 Hom.: 2316 Cov.: 33

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0829

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.163 AC: 24748 AN: 152174 Hom.: 2328 Cov.: 33 AF XY: 0.161 AC XY: 11972 AN XY: 74392

African (AFR) AF: 0.0789 AC: 3279 AN: 41544

American (AMR) AF: 0.209 AC: 3200 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 540 AN: 3470

East Asian (EAS) AF: 0.0826 AC: 426 AN: 5160

South Asian (SAS) AF: 0.153 AC: 736 AN: 4824

European-Finnish (FIN) AF: 0.165 AC: 1745 AN: 10588

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14313 AN: 67978

Other (OTH) AF: 0.179 AC: 379 AN: 2112

Alfa AF: 0.199 Hom.: 5241

Bravo AF: 0.162

Asia WGS AF: 0.163 AC: 566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.70
PhyloP100		-0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17702471; hg19: chr13-93877117;