rs2149065

Positions:

• chr13-92435923-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004466.6(GPC5):​c.1561+290934G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,948 control chromosomes in the GnomAD database, including 7,669 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 0.30 (7669 hom., cov: 33)
• Consequence: GPC5 NM_004466.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC5	NM_004466.6	c.1561+290934G>A		intron_variant		ENST00000377067.9	NP_004457.1
GPC5	XM_017020435.3	c.1561+290934G>A		intron_variant			XP_016875924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC5	ENST00000377067.9	c.1561+290934G>A		intron_variant		1	NM_004466.6	ENSP00000366267	P1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44983 AN: 151830 Hom.: 7642 Cov.: 33

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.297 AC: 45070 AN: 151948 Hom.: 7669 Cov.: 33 AF XY: 0.301 AC XY: 22360 AN XY: 74252

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.281

Alfa AF: 0.237 Hom.: 2126

Bravo AF: 0.314

Asia WGS AF: 0.442 AC: 1531 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs2149065; hg19: chr13-93088176;