rs17251454

Positions:

• chrX-133548093-T-C

Variant summary

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

The NM_004484.4(GPC3):​c.1574-11800A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 112,565 control chromosomes in the GnomAD database, including 10 homozygotes. There are 501 hemizygotes in GnomAD. 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 0.014 (10 hom., 501 hem., cov: 23)
• Consequence: GPC3 NM_004484.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

Genes affected

GPC3 (HGNC:4451): (glypican 3) 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. The protein encoded by this gene can bind to and inhibit the dipeptidyl peptidase activity of CD26, and it can induce apoptosis in certain cell types. Deletion mutations in this gene are associated with Simpson-Golabi-Behmel syndrome, also known as Simpson dysmorphia syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

GPC3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0136 (1532/112565) while in subpopulation NFE AF= 0.0178 (948/53378). AF 95% confidence interval is 0.0168. There are 10 homozygotes in gnomad4. There are 501 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC3	NM_004484.4	c.1574-11800A>G		intron_variant		ENST00000370818.8	NP_004475.1
GPC3	NM_001164617.2	c.1643-11800A>G		intron_variant			NP_001158089.1
GPC3	NM_001164618.2	c.1526-11800A>G		intron_variant			NP_001158090.1
GPC3	NM_001164619.2	c.1412-11800A>G		intron_variant			NP_001158091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC3	ENST00000370818.8	c.1574-11800A>G		intron_variant		1	NM_004484.4	ENSP00000359854.3

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 1532 AN: 112513 Hom.: 10 Cov.: 23 AF XY: 0.0144 AC XY: 500 AN XY: 34663

Gnomad AFR AF: 0.00210

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00772

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0151

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

GnomAD4 genome AF: 0.0136 AC: 1532 AN: 112565 Hom.: 10 Cov.: 23 AF XY: 0.0144 AC XY: 501 AN XY: 34725

Gnomad4 AFR AF: 0.00210

Gnomad4 AMR AF: 0.0134

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00811

Gnomad4 FIN AF: 0.0317

Gnomad4 NFE AF: 0.0178

Gnomad4 OTH AF: 0.0150

Alfa AF: 0.0163 Hom.: 121

Bravo AF: 0.0118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.0
DANN	Benign	0.57

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: rs17251454; hg19: chrX-132682121;