Variant chr2-240462311-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002081.3(GPC1):c.446G>A(p.Arg149His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,607,692 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00099 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

GPC1
NM_002081.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.92

Variant links:

Genes affected

GPC1 (HGNC:4449): (glypican 1) 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. [provided by RefSeq, Jul 2008]

GPC1 links:

GPC1 (HGNC:):

GPC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012554258).

BP6

Variant 2-240462311-G-A is Benign according to our data. Variant chr2-240462311-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 725099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC1	NM_002081.3 linkuse as main transcript	c.446G>A	p.Arg149His	missense_variant	3/9	ENST00000264039.7	NP_002072.2	P35052-1A0A384NPH9
GPC1	XM_047443961.1 linkuse as main transcript	c.230G>A	p.Arg77His	missense_variant	3/9		XP_047299917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC1	ENST00000264039.7 linkuse as main transcript	c.446G>A	p.Arg149His	missense_variant	3/9	1	NM_002081.3	ENSP00000264039.2		P35052-1

Frequencies

GnomAD3 genomes

AF:

0.000992

AC:

151

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00299

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000757

AC:

179

AN:

236372

Hom.:

AF XY:

0.000644

AC XY:

AN XY:

128820

show subpopulations

Gnomad AFR exome

AF:

0.00321

Gnomad AMR exome

AF:

0.00373

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000340

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000473

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.000198

AC:

288

AN:

1455390

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

137

AN XY:

723582

show subpopulations

Gnomad4 AFR exome

AF:

0.00288

Gnomad4 AMR exome

AF:

0.00342

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000351

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.000250

GnomAD4 genome

AF:

0.000991

AC:

151

AN:

152302

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00298

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000278

Hom.:

Bravo

AF:

0.00122

ESP6500AA

AF:

0.00229

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000654

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;T;.;.;T

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.80

T;T;T;D;T

M_CAP

Benign

0.067

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.8

M;.;.;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.6

D;N;D;D;.

REVEL

Benign

0.23

Sift

Benign

0.082

T;D;T;T;.

Sift4G

Benign

0.070

T;T;T;D;T

Polyphen

0.75

P;.;.;.;.

Vest4

0.33

MVP

0.90

MPC

0.48

ClinPred

0.062

GERP RS

3.1

Varity_R

0.46

gMVP

0.53

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