rs727986

Variant names:

• chr13-92559086-A-G
• rs727986
• NM_004466.6:c.1562-307196A>G

Variant summary

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

The NM_004466.6(GPC5):​c.1562-307196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,712 control chromosomes in the GnomAD database, including 6,925 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 0.29 (6925 hom., cov: 31)
• Consequence: GPC5 NM_004466.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 3 publications found

Genes affected

GPC5 (HGNC:4453): (glypican 5) Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC5	NM_004466.6	c.1562-307196A>G		intron_variant	Intron 7 of 7	ENST00000377067.9	NP_004457.1
GPC5	XM_017020435.3	c.1562-190878A>G		intron_variant	Intron 7 of 7		XP_016875924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC5	ENST00000377067.9	c.1562-307196A>G		intron_variant	Intron 7 of 7	1	NM_004466.6	ENSP00000366267.3

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44094 AN: 151594 Hom.: 6908 Cov.: 31

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.291 AC: 44139 AN: 151712 Hom.: 6925 Cov.: 31 AF XY: 0.284 AC XY: 21054 AN XY: 74086

African (AFR) AF: 0.414 AC: 17128 AN: 41390

American (AMR) AF: 0.221 AC: 3359 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3468

East Asian (EAS) AF: 0.194 AC: 992 AN: 5122

South Asian (SAS) AF: 0.230 AC: 1103 AN: 4804

European-Finnish (FIN) AF: 0.258 AC: 2717 AN: 10524

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17395 AN: 67864

Other (OTH) AF: 0.260 AC: 548 AN: 2106

Alfa AF: 0.259 Hom.: 2330

Bravo AF: 0.294

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.6
DANN	Benign	0.75
PhyloP100		-0.13
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: rs727986; hg19: chr13-93211339;