rs462954

chr13-91718836-A-G

Variant summary

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

The NM_004466.6(GPC5):c.1021-9696A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 151,968 control chromosomes in the GnomAD database, including 2,216 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 0.16 (2216 hom., cov: 32)
• Consequence: GPC5 NM_004466.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC5	NM_004466.6	c.1021-9696A>G		intron_variant		ENST00000377067.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC5	ENST00000377067.9	c.1021-9696A>G		intron_variant		1	NM_004466.6	P1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24085 AN: 151850 Hom.: 2211 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.159 AC: 24119 AN: 151968 Hom.: 2216 Cov.: 32 AF XY: 0.160 AC XY: 11861 AN XY: 74292

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0993

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.176

Alfa AF: 0.124 Hom.: 925

Bravo AF: 0.169

Asia WGS AF: 0.242 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.7
Dann	Benign	0.75

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: rs462954; hg19: chr13-92371090;