rs17317322

Variant names:

• chrX-133359600-C-T
• rs17317322
• NM_001448.3:c.161-20259G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001448.3(GPC4):​c.161-20259G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 111,577 control chromosomes in the GnomAD database, including 56 homozygotes. There are 999 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 0.031 (56 hom., 999 hem., cov: 22)
• Consequence: GPC4 NM_001448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88
• Publications: 0 publications found

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]

GPC4 Gene-Disease associations (from GenCC):

• Keipert syndrome

  Inheritance: XL, XLR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0307 (3424/111577) while in subpopulation SAS AF = 0.0395 (104/2631). AF 95% confidence interval is 0.035. There are 56 homozygotes in GnomAd4. There are 999 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 56 XL,XLR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC4	NM_001448.3	c.161-20259G>A		intron_variant	Intron 1 of 8	ENST00000370828.4	NP_001439.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC4	ENST00000370828.4	c.161-20259G>A		intron_variant	Intron 1 of 8	1	NM_001448.3	ENSP00000359864.3

Frequencies

GnomAD3 genomes AF: 0.0307 AC: 3424 AN: 111521 Hom.: 56 Cov.: 22

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.0568

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.00113

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.0471

Gnomad MID AF: 0.0339

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0430

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

GnomAD4 genome AF: 0.0307 AC: 3424 AN: 111577 Hom.: 56 Cov.: 22 AF XY: 0.0296 AC XY: 999 AN XY: 33747

African (AFR) AF: 0.0223 AC: 687 AN: 30773

American (AMR) AF: 0.0235 AC: 247 AN: 10529

Ashkenazi Jewish (ASJ) AF: 0.0230 AC: 61 AN: 2647

East Asian (EAS) AF: 0.00114 AC: 4 AN: 3524

South Asian (SAS) AF: 0.0395 AC: 104 AN: 2631

European-Finnish (FIN) AF: 0.0471 AC: 282 AN: 5983

Middle Eastern (MID) AF: 0.0372 AC: 8 AN: 215

European-Non Finnish (NFE) AF: 0.0363 AC: 1927 AN: 53058

Other (OTH) AF: 0.0425 AC: 65 AN: 1530

Alfa AF: 0.0339 Hom.: 233

Bravo AF: 0.0305

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.68
PhyloP100		2.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs17317322; hg19: chrX-132493628;