rs1413191

Positions:

• chr13-92561223-C-T

Variant summary

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

The NM_004466.6(GPC5):​c.1562-305059C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 151,788 control chromosomes in the GnomAD database, including 2,865 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 0.20 (2865 hom., cov: 32)
• Consequence: GPC5 NM_004466.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC5	NM_004466.6	c.1562-305059C>T		intron_variant		ENST00000377067.9	NP_004457.1
GPC5	XM_017020435.3	c.1562-188741C>T		intron_variant			XP_016875924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC5	ENST00000377067.9	c.1562-305059C>T		intron_variant		1	NM_004466.6	ENSP00000366267	P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29597 AN: 151670 Hom.: 2860 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.195 AC: 29612 AN: 151788 Hom.: 2865 Cov.: 32 AF XY: 0.192 AC XY: 14215 AN XY: 74172

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.177

Alfa AF: 0.202 Hom.: 5182

Bravo AF: 0.194

Asia WGS AF: 0.199 AC: 693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.71

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: rs1413191; hg19: chr13-93213476;