rs5977860

Variant names:

• chrX-133348166-C-T
• rs5977860
• NM_001448.3:c.161-8825G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001448.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC4	NM_001448.3	MANE Select	c.161-8825G>A		intron	N/A	NP_001439.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC4	ENST00000370828.4	TSL:1 MANE Select	c.161-8825G>A		intron	N/A	ENSP00000359864.3

Frequencies

GnomAD3 genomes AF: 0.471 AC: 52478 AN: 111308 Hom.: 11269 Cov.: 23

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

African (AFR) AF: 0.852 AC: 26094 AN: 30627

American (AMR) AF: 0.285 AC: 3016 AN: 10574

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 917 AN: 2645

East Asian (EAS) AF: 0.435 AC: 1529 AN: 3518

South Asian (SAS) AF: 0.546 AC: 1435 AN: 2627

European-Finnish (FIN) AF: 0.273 AC: 1625 AN: 5943

Middle Eastern (MID) AF: 0.347 AC: 75 AN: 216

European-Non Finnish (NFE) AF: 0.318 AC: 16846 AN: 53025

Other (OTH) AF: 0.455 AC: 689 AN: 1514

Alfa AF: 0.398 Hom.: 2871

Bravo AF: 0.486

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.017
DANN	Benign	0.45
PhyloP100		-1.1
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: rs5977860; hg19: chrX-132482194;