rs3814277

Variant names:

• chr13-93327090-C-G
• rs3814277
• NM_005708.5:c.160+99474C>G

Variant summary

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

The NM_005708.5(GPC6):​c.160+99474C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,096 control chromosomes in the GnomAD database, including 1,472 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 0.12 (1472 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 1 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.160+99474C>G		intron_variant	Intron 1 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_047429990.1	c.-51+100408C>G		intron_variant	Intron 1 of 8		XP_047285946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.160+99474C>G		intron_variant	Intron 1 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18587 AN: 151976 Hom.: 1468 Cov.: 32

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0993

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.122 AC: 18602 AN: 152096 Hom.: 1472 Cov.: 32 AF XY: 0.129 AC XY: 9601 AN XY: 74342

African (AFR) AF: 0.0851 AC: 3535 AN: 41524

American (AMR) AF: 0.213 AC: 3257 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1878 AN: 5146

South Asian (SAS) AF: 0.152 AC: 731 AN: 4820

European-Finnish (FIN) AF: 0.160 AC: 1685 AN: 10558

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0993 AC: 6749 AN: 67986

Other (OTH) AF: 0.127 AC: 268 AN: 2116

Alfa AF: 0.108 Hom.: 139

Bravo AF: 0.128

Asia WGS AF: 0.219 AC: 761 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.5
DANN	Benign	0.63
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3814277; hg19: chr13-93979343;