rs5977860

chrX-133348166-C-T

Variant summary

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

The NM_001448.3(GPC4):c.161-8825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 111,360 control chromosomes in the GnomAD database, including 11,275 homozygotes. There are 15,328 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 0.47 (11275 hom., 15328 hem., cov: 23)
• Consequence: GPC4 NM_001448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC4	NM_001448.3	c.161-8825G>A		intron_variant		ENST00000370828.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC4	ENST00000370828.4	c.161-8825G>A		intron_variant		1	NM_001448.3	P1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 52478 AN: 111308 Hom.: 11269 Cov.: 23 AF XY: 0.455 AC XY: 15271 AN XY: 33528

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.472 AC: 52533 AN: 111360 Hom.: 11275 Cov.: 23 AF XY: 0.456 AC XY: 15328 AN XY: 33590

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.455

Alfa AF: 0.398 Hom.: 2871

Bravo AF: 0.486

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.017
Dann	Benign	0.45

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: rs5977860; hg19: chrX-132482194;