Variant rs1048369 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001448.3(GPC4):c.1325C>T(p.Ala442Val) variant causes a missense change. The variant allele was found at a frequency of 0.312 in 1,206,963 control chromosomes in the GnomAD database, including 42,163 homozygotes. There are 125,172 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.38 ( 6635 hom., 11938 hem., cov: 22)

Exomes 𝑓: 0.31 ( 35528 hom. 113234 hem. )

Consequence

GPC4
NM_001448.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.92

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4469028E-4).

BP6

Variant X-133303309-G-A is Benign according to our data. Variant chrX-133303309-G-A is described in ClinVar as [Benign]. Clinvar id is 1285303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC4	NM_001448.3 linkuse as main transcript	c.1325C>T	p.Ala442Val	missense_variant	8/9	ENST00000370828.4	NP_001439.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC4	ENST00000370828.4 linkuse as main transcript	c.1325C>T	p.Ala442Val	missense_variant	8/9	1	NM_001448.3	ENSP00000359864	P1	O75487-1

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

42064

AN:

110248

Hom.:

6633

Cov.:

AF XY:

0.366

AC XY:

11909

AN XY:

32520

show subpopulations

Gnomad AFR

AF:

0.594

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.443

Gnomad SAS

AF:

0.490

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.369

GnomAD3 exomes

AF:

0.330

AC:

59799

AN:

181319

Hom.:

7078

AF XY:

0.339

AC XY:

22333

AN XY:

65925

show subpopulations

Gnomad AFR exome

AF:

0.599

Gnomad AMR exome

AF:

0.179

Gnomad ASJ exome

AF:

0.369

Gnomad EAS exome

AF:

0.444

Gnomad SAS exome

AF:

0.503

Gnomad FIN exome

AF:

0.246

Gnomad NFE exome

AF:

0.292

Gnomad OTH exome

AF:

0.307

GnomAD4 exome

AF:

0.305

AC:

334730

AN:

1096658

Hom.:

35528

Cov.:

AF XY:

0.312

AC XY:

113234

AN XY:

362400

show subpopulations

Gnomad4 AFR exome

AF:

0.607

Gnomad4 AMR exome

AF:

0.187

Gnomad4 ASJ exome

AF:

0.363

Gnomad4 EAS exome

AF:

0.399

Gnomad4 SAS exome

AF:

0.498

Gnomad4 FIN exome

AF:

0.255

Gnomad4 NFE exome

AF:

0.284

Gnomad4 OTH exome

AF:

0.339

GnomAD4 genome

AF:

0.382

AC:

42091

AN:

110305

Hom.:

6635

Cov.:

AF XY:

0.366

AC XY:

11938

AN XY:

32587

show subpopulations

Gnomad4 AFR

AF:

0.594

Gnomad4 AMR

AF:

0.255

Gnomad4 ASJ

AF:

0.369

Gnomad4 EAS

AF:

0.443

Gnomad4 SAS

AF:

0.492

Gnomad4 FIN

AF:

0.240

Gnomad4 NFE

AF:

0.293

Gnomad4 OTH

AF:

0.367

Alfa

AF:

0.316

Hom.:

29736

Bravo

AF:

0.389

TwinsUK

AF:

0.276

AC:

1023

ALSPAC

AF:

0.288

AC:

831

ESP6500AA

AF:

0.597

AC:

2290

ESP6500EA

AF:

0.295

AC:

1986

ExAC

AF:

0.349

AC:

42354

EpiCase

AF:

0.301

EpiControl

AF:

0.299

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Keipert syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

MetaRNN

Benign

0.00014

MetaSVM

Benign

-0.91

MutationAssessor

Benign

2.0

MutationTaster

Benign

0.0000011

P;P

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.21

Sift

Benign

0.099

Sift4G

Benign

0.067

Polyphen

0.90

Vest4

0.063

MPC

1.5

ClinPred

0.030

GERP RS

4.7

Varity_R

0.15

gMVP

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over