rs1041073

Positions:

chr13-31317609-G-A

Variant summary

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

The NM_194318.4(B3GLCT):c.1108G>A(p.Glu370Lys) variant causes a missense change. The variant allele was found at a frequency of 0.748 in 1,613,678 control chromosomes in the GnomAD database, including 456,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 36183 hom., cov: 31)

Exomes 𝑓: 0.76 ( 420551 hom. )

Consequence

B3GLCT
NM_194318.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 6.17

Variant links:

Genes affected

B3GLCT (HGNC:20207): (beta 3-glucosyltransferase) The protein encoded by this gene is a beta-1,3-glucosyltransferase that transfers glucose to O-linked fucosylglycans on thrombospondin type-1 repeats (TSRs) of several proteins. The encoded protein is a type II membrane protein. Defects in this gene are a cause of Peters-plus syndrome (PPS).[provided by RefSeq, Mar 2009]

B3GLCT 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=2.169308E-6).

BP6

Variant 13-31317609-G-A is Benign according to our data. Variant chr13-31317609-G-A is described in ClinVar as [Benign]. Clinvar id is 96624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-31317609-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GLCT	NM_194318.4 linkuse as main transcript	c.1108G>A	p.Glu370Lys	missense_variant	13/15	ENST00000343307.5	NP_919299.3	Q6Y288

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GLCT	ENST00000343307.5 linkuse as main transcript	c.1108G>A	p.Glu370Lys	missense_variant	13/15	1	NM_194318.4	ENSP00000343002.4		Q6Y288

Frequencies

GnomAD3 genomes

AF:

0.671

AC:

101919

AN:

151882

Hom.:

36180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.873

Gnomad AMR

AF:

0.752

Gnomad ASJ

AF:

0.830

Gnomad EAS

AF:

0.779

Gnomad SAS

AF:

0.768

Gnomad FIN

AF:

0.710

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.773

Gnomad OTH

AF:

0.707

GnomAD3 exomes

AF:

0.749

AC:

188293

AN:

251428

Hom.:

71729

AF XY:

0.756

AC XY:

102745

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.405

Gnomad AMR exome

AF:

0.792

Gnomad ASJ exome

AF:

0.837

Gnomad EAS exome

AF:

0.786

Gnomad SAS exome

AF:

0.760

Gnomad FIN exome

AF:

0.714

Gnomad NFE exome

AF:

0.774

Gnomad OTH exome

AF:

0.761

GnomAD4 exome

AF:

0.756

AC:

1105023

AN:

1461678

Hom.:

420551

Cov.:

AF XY:

0.758

AC XY:

551507

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.401

Gnomad4 AMR exome

AF:

0.787

Gnomad4 ASJ exome

AF:

0.838

Gnomad4 EAS exome

AF:

0.758

Gnomad4 SAS exome

AF:

0.762

Gnomad4 FIN exome

AF:

0.710

Gnomad4 NFE exome

AF:

0.766

Gnomad4 OTH exome

AF:

0.745

GnomAD4 genome

AF:

0.671

AC:

101952

AN:

152000

Hom.:

36183

Cov.:

AF XY:

0.673

AC XY:

49994

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.417

Gnomad4 AMR

AF:

0.752

Gnomad4 ASJ

AF:

0.830

Gnomad4 EAS

AF:

0.779

Gnomad4 SAS

AF:

0.767

Gnomad4 FIN

AF:

0.710

Gnomad4 NFE

AF:

0.773

Gnomad4 OTH

AF:

0.708

Alfa

AF:

0.755

Hom.:

78531

Bravo

AF:

0.663

TwinsUK

AF:

0.767

AC:

2843

ALSPAC

AF:

0.773

AC:

2978

ESP6500AA

AF:

0.416

AC:

1833

ESP6500EA

AF:

0.778

AC:

6691

ExAC

AF:

0.742

AC:

90132

Asia WGS

AF:

0.782

AC:

2718

AN:

3478

EpiCase

AF:

0.774

EpiControl

AF:

0.781

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 10, 2014	- -

Peters plus syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

Eigen

Benign

-0.035

Eigen_PC

Benign

-0.080

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0000022

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.8

REVEL

Benign

0.29

Sift

Benign

0.13

Sift4G

Benign

0.29

Polyphen

0.96

Vest4

0.26

MPC

0.34

ClinPred

0.034

GERP RS

3.2

Varity_R

0.098

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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