rs17430373

Positions:

• chr13-92312559-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004466.6(GPC5):​c.1561+167570A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 152,258 control chromosomes in the GnomAD database, including 52 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 0.021 (52 hom., cov: 33)
• Consequence: GPC5 NM_004466.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797

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=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0214 (3253/152258) while in subpopulation NFE AF= 0.0355 (2413/67982). AF 95% confidence interval is 0.0343. There are 52 homozygotes in gnomad4. There are 1474 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC5	NM_004466.6	c.1561+167570A>G		intron_variant		ENST00000377067.9	NP_004457.1
GPC5	XM_017020435.3	c.1561+167570A>G		intron_variant			XP_016875924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC5	ENST00000377067.9	c.1561+167570A>G		intron_variant		1	NM_004466.6	ENSP00000366267.3

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3252 AN: 152140 Hom.: 52 Cov.: 33

Gnomad AFR AF: 0.00647

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0214 AC: 3253 AN: 152258 Hom.: 52 Cov.: 33 AF XY: 0.0198 AC XY: 1474 AN XY: 74442

Gnomad4 AFR AF: 0.00645

Gnomad4 AMR AF: 0.0159

Gnomad4 ASJ AF: 0.00835

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.0191

Gnomad4 NFE AF: 0.0355

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0289 Hom.: 16

Bravo AF: 0.0202

Asia WGS AF: 0.00320 AC: 11 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.60
DANN	Benign	0.79

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: rs17430373; hg19: chr13-92964812;