chrX-133336655-A-G

Position:

• chrX-133336655-A-G

Variant summary

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

The NM_001448.3(GPC4):​c.319+2528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 109,947 control chromosomes in the GnomAD database, including 6,447 homozygotes. There are 11,388 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 0.37 (6447 hom., 11388 hem., cov: 21)
• Consequence: GPC4 NM_001448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336

Genes affected

GPC4 (HGNC:4452): (glypican 4) 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 GPC4 gene is adjacent to the 3' end of GPC3 and may also play a role in Simpson-Golabi-Behmel syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC4	NM_001448.3	c.319+2528T>C		intron_variant		ENST00000370828.4	NP_001439.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC4	ENST00000370828.4	c.319+2528T>C		intron_variant		1	NM_001448.3	ENSP00000359864.3

Frequencies

GnomAD3 genomes AF: 0.371 AC: 40746 AN: 109894 Hom.: 6443 Cov.: 21 AF XY: 0.353 AC XY: 11362 AN XY: 32190

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.308

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.371 AC: 40770 AN: 109947 Hom.: 6447 Cov.: 21 AF XY: 0.353 AC XY: 11388 AN XY: 32253

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.350

Alfa AF: 0.310 Hom.: 3481

Bravo AF: 0.381

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.75

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: rs41537046; hg19: chrX-132470683;