Variant 9-33113324-C-T 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_001497.4(B4GALT1):c.*130G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,397,874 control chromosomes in the GnomAD database, including 14,944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1821 hom., cov: 33)

Exomes 𝑓: 0.12 ( 13123 hom. )

Consequence

B4GALT1
NM_001497.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.09

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:

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 (BayesDel_noAF=-0.53).

BP6

Variant 9-33113324-C-T is Benign according to our data. Variant chr9-33113324-C-T is described in ClinVar as [Benign]. Clinvar id is 1289695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALT1	NM_001497.4 linkuse as main transcript	c.*130G>A		3_prime_UTR_variant	6/6	ENST00000379731.5	NP_001488.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B4GALT1	ENST00000379731.5 linkuse as main transcript	c.*130G>A		3_prime_UTR_variant	6/6	1	NM_001497.4	ENSP00000369055	P1	P15291-1
B4GALT1	ENST00000535206.5 linkuse as main transcript	c.649-8543G>A		intron_variant		1		ENSP00000440341

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20485

AN:

152076

Hom.:

1822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.0396

Gnomad AMR

AF:

0.0848

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.477

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.118

GnomAD4 exome

AF:

0.125

AC:

155411

AN:

1245680

Hom.:

13123

Cov.:

AF XY:

0.129

AC XY:

80804

AN XY:

628538

show subpopulations

Gnomad4 AFR exome

AF:

0.159

Gnomad4 AMR exome

AF:

0.0539

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.452

Gnomad4 SAS exome

AF:

0.243

Gnomad4 FIN exome

AF:

0.119

Gnomad4 NFE exome

AF:

0.103

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.135

AC:

20492

AN:

152194

Hom.:

1821

Cov.:

AF XY:

0.140

AC XY:

10416

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.0846

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.477

Gnomad4 SAS

AF:

0.261

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.118

Alfa

AF:

0.108

Hom.:

1385

Bravo

AF:

0.129

Asia WGS

AF:

0.320

AC:

1107

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.90

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