rs17430373

Variant names:

• chr13-92312559-A-G
• rs17430373
• NM_004466.6:c.1561+167570A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC5	NM_004466.6	c.1561+167570A>G		intron_variant	Intron 7 of 7	ENST00000377067.9	NP_004457.1
GPC5	XM_017020435.3	c.1561+167570A>G		intron_variant	Intron 7 of 7		XP_016875924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC5	ENST00000377067.9	c.1561+167570A>G		intron_variant	Intron 7 of 7	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

African (AFR) AF: 0.00645 AC: 268 AN: 41576

American (AMR) AF: 0.0159 AC: 243 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.0191 AC: 203 AN: 10612

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0355 AC: 2413 AN: 67982

Other (OTH) AF: 0.0260 AC: 55 AN: 2114

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
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17430373; hg19: chr13-92964812;