rs1041073

chr13-31317609-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 6.17

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]

ACMG classification

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	UniProt
B3GLCT	NM_194318.4	c.1108G>A	p.Glu370Lys	missense_variant	13/15	ENST00000343307.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GLCT	ENST00000343307.5	c.1108G>A	p.Glu370Lys	missense_variant	13/15	1	NM_194318.4	P1

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101919 AN: 151882 Hom.: 36180 Cov.: 31

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

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.: 50 AF XY: 0.758 AC XY: 551507 AN XY: 727158

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.: 31 AF XY: 0.673 AC XY: 49994 AN XY: 74294

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:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

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

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	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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not provided Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.035
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0000022	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.00069	P
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.29
Sift	Benign	0.13	T
Sift4G	Benign	0.29	T
Polyphen		0.96	D
Vest4		0.26
MPC		0.34
ClinPred		0.034	T
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

Other links and lift over

dbSNP: rs1041073; hg19: chr13-31891746;