rs7998314

Variant names:

• chr13-93580876-A-C
• rs7998314
• NM_005708.5:c.319+35455A>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.319+35455A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,054 control chromosomes in the GnomAD database, including 44,533 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 0.76 (44533 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.319+35455A>C		intron_variant	Intron 2 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_017020300.2	c.109+35455A>C		intron_variant	Intron 2 of 8		XP_016875789.1
GPC6	XM_047429990.1	c.109+35455A>C		intron_variant	Intron 2 of 8		XP_047285946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.319+35455A>C		intron_variant	Intron 2 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115428 AN: 151938 Hom.: 44509 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.760 AC: 115497 AN: 152054 Hom.: 44533 Cov.: 32 AF XY: 0.755 AC XY: 56154 AN XY: 74332

African (AFR) AF: 0.723 AC: 29948 AN: 41436

American (AMR) AF: 0.681 AC: 10394 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2766 AN: 3472

East Asian (EAS) AF: 0.393 AC: 2037 AN: 5178

South Asian (SAS) AF: 0.667 AC: 3213 AN: 4814

European-Finnish (FIN) AF: 0.848 AC: 8968 AN: 10570

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55590 AN: 67996

Other (OTH) AF: 0.752 AC: 1585 AN: 2108

Alfa AF: 0.793 Hom.: 127269

Bravo AF: 0.739

Asia WGS AF: 0.573 AC: 1977 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.65
PhyloP100		0.16
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: rs7998314; hg19: chr13-94233129;