rs342693

chr13-91704978-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.1020+11097A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,084 control chromosomes in the GnomAD database, including 5,051 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 0.22 (5051 hom., cov: 32)
• Consequence: GPC5 NM_004466.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC5	NM_004466.6	c.1020+11097A>G		intron_variant		ENST00000377067.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC5	ENST00000377067.9	c.1020+11097A>G		intron_variant		1	NM_004466.6	P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33852 AN: 151966 Hom.: 5033 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0976

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.223 AC: 33918 AN: 152084 Hom.: 5051 Cov.: 32 AF XY: 0.221 AC XY: 16448 AN XY: 74364

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.0976

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.230

Alfa AF: 0.153 Hom.: 2814

Bravo AF: 0.240

Asia WGS AF: 0.240 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.19
Dann	Benign	0.73

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: rs342693; hg19: chr13-92357232;