rs17233815

chr13-92706621-T-C

Variant summary

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

The NM_004466.6(GPC5):c.1562-159661T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 152,152 control chromosomes in the GnomAD database, including 438 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 0.045 (438 hom., cov: 32)
• Consequence: GPC5 NM_004466.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416

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]

GPC5-AS1 (HGNC:39886): (GPC5 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC5	NM_004466.6	c.1562-159661T>C		intron_variant		ENST00000377067.9
GPC5-AS1	NR_046520.1	n.167-562A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC5	ENST00000377067.9	c.1562-159661T>C		intron_variant		1	NM_004466.6	P1
GPC5-AS1	ENST00000419288.1	n.167-562A>G		intron_variant, non_coding_transcript_variant		3
GPC5-AS1	ENST00000451897.5	n.154-562A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6868 AN: 152034 Hom.: 435 Cov.: 32

Gnomad AFR AF: 0.00743

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.0958

Gnomad FIN AF: 0.0936

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0276

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0452 AC: 6878 AN: 152152 Hom.: 438 Cov.: 32 AF XY: 0.0511 AC XY: 3801 AN XY: 74374

Gnomad4 AFR AF: 0.00741

Gnomad4 AMR AF: 0.0923

Gnomad4 ASJ AF: 0.0655

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.0963

Gnomad4 FIN AF: 0.0936

Gnomad4 NFE AF: 0.0277

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0381 Hom.: 104

Bravo AF: 0.0469

Asia WGS AF: 0.170 AC: 593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.1
Dann	Benign	0.80

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: rs17233815; hg19: chr13-93358874;