9-33167143-G-T

Position:

chr9-33167143-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001497.4(B4GALT1):c.27C>A(p.Ser9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000364 in 1,601,068 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

B4GALT1
NM_001497.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.46

Variant links:

Genes affected

B4GALT1 (HGNC:924): (beta-1,4-galactosyltransferase 1) This gene is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes. They encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose; all transfer galactose in a beta1,4 linkage to similar acceptor sugars: GlcNAc, Glc, and Xyl. Each beta4GalT has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus and which then remains uncleaved to function as a transmembrane anchor. By sequence similarity, the beta4GalTs form four groups: beta4GalT1 and beta4GalT2, beta4GalT3 and beta4GalT4, beta4GalT5 and beta4GalT6, and beta4GalT7. This gene is unique among the beta4GalT genes because it encodes an enzyme that participates both in glycoconjugate and lactose biosynthesis. For the first activity, the enzyme adds galactose to N-acetylglucosamine residues that are either monosaccharides or the nonreducing ends of glycoprotein carbohydrate chains. The second activity is restricted to lactating mammary tissues where the enzyme forms a heterodimer with alpha-lactalbumin to catalyze UDP-galactose + D-glucose <=> UDP + lactose. The two enzymatic forms result from alternate transcription initiation sites and post-translational processing. Two transcripts, which differ only at the 5' end, with approximate lengths of 4.1 kb and 3.9 kb encode the same protein. The longer transcript encodes the type II membrane-bound, trans-Golgi resident protein involved in glycoconjugate biosynthesis. The shorter transcript encodes a protein which is cleaved to form the soluble lactose synthase. [provided by RefSeq, Jul 2008]

B4GALT1 links:

B4GALT1-AS1 (HGNC:):

B4GALT1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061349273).

BP6

Variant 9-33167143-G-T is Benign according to our data. Variant chr9-33167143-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 790066.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALT1	NM_001497.4 linkuse as main transcript	c.27C>A	p.Ser9Arg	missense_variant	1/6	ENST00000379731.5	NP_001488.2	P15291-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
B4GALT1	ENST00000379731.5 linkuse as main transcript	c.27C>A	p.Ser9Arg	missense_variant	1/6	1	NM_001497.4	ENSP00000369055.4	P15291-1
B4GALT1	ENST00000535206.5 linkuse as main transcript	c.27C>A	p.Ser9Arg	missense_variant	1/3	1		ENSP00000440341.1	Q86XA6
B4GALT1-AS1	ENST00000426270.5 linkuse as main transcript	n.72+97G>T		intron_variant		2
B4GALT1-AS1	ENST00000654325.1 linkuse as main transcript	n.99+97G>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00218

AC:

332

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00779

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000373

AC:

AN:

214468

Hom.:

AF XY:

0.000318

AC XY:

AN XY:

119636

show subpopulations

Gnomad AFR exome

AF:

0.00651

Gnomad AMR exome

AF:

0.0000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000173

AC:

250

AN:

1448750

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

105

AN XY:

720196

show subpopulations

Gnomad4 AFR exome

AF:

0.00691

Gnomad4 AMR exome

AF:

0.0000914

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.000251

GnomAD4 genome

AF:

0.00218

AC:

332

AN:

152318

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

158

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00777

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000462

Hom.:

Bravo

AF:

0.00217

ESP6500AA

AF:

0.00378

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000479

AC:

Asia WGS

AF:

0.000580

AC:

AN:

3464

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

B4GALT1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0094

T;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.68

T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.0061

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

.;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.83

N;N

REVEL

Benign

0.037

Sift

Uncertain

0.020

D;D

Sift4G

Benign

0.091

T;T

Polyphen

0.23

.;B

Vest4

0.097

MutPred

0.32

Gain of MoRF binding (P = 6e-04);Gain of MoRF binding (P = 6e-04);

MVP

0.71

MPC

0.57

ClinPred

0.078

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.34

gMVP

0.59

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