9-33113324-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

26 publications found

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 Gene-Disease associations (from GenCC):

B4GALT1-congenital disorder of glycosylation
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics

B4GALT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001497.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
B4GALT1	NM_001497.4	MANE Select	c.*130G>A	3_prime_UTR	Exon 6 of 6	NP_001488.2
B4GALT1	NM_001378495.1		c.*130G>A	3_prime_UTR	Exon 6 of 6	NP_001365424.1	P15291-2
B4GALT1	NM_001378496.1		c.*130G>A	3_prime_UTR	Exon 5 of 5	NP_001365425.1	W6MEN3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
B4GALT1	ENST00000379731.5	TSL:1 MANE Select	c.*130G>A	3_prime_UTR	Exon 6 of 6	ENSP00000369055.4	P15291-1
B4GALT1	ENST00000535206.6	TSL:1	c.649-8543G>A	intron	N/A	ENSP00000440341.1	Q86XA6
B4GALT1	ENST00000860372.1		c.*130G>A	3_prime_UTR	Exon 7 of 7	ENSP00000530431.1

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

African (AFR)

AF:

0.159

AC:

4608

AN:

29064

American (AMR)

AF:

0.0539

AC:

2331

AN:

43266

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

2520

AN:

24552

East Asian (EAS)

AF:

0.452

AC:

17378

AN:

38424

South Asian (SAS)

AF:

0.243

AC:

19620

AN:

80608

European-Finnish (FIN)

AF:

0.119

AC:

6267

AN:

52692

Middle Eastern (MID)

AF:

0.133

AC:

503

AN:

3784

European-Non Finnish (NFE)

AF:

0.103

AC:

94905

AN:

920182

Other (OTH)

AF:

0.137

AC:

7279

AN:

53108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6747

13495

20242

26990

33737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3492

6984

10476

13968

17460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.135

AC:

20492

AN:

152194

Hom.:

1821

Cov.:

AF XY:

0.140

AC XY:

10416

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.159

AC:

6616

AN:

41504

American (AMR)

AF:

0.0846

AC:

1294

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

351

AN:

3472

East Asian (EAS)

AF:

0.477

AC:

2465

AN:

5172

South Asian (SAS)

AF:

0.261

AC:

1256

AN:

4820

European-Finnish (FIN)

AF:

0.119

AC:

1260

AN:

10608

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6931

AN:

68004

Other (OTH)

AF:

0.118

AC:

249

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

849

1698

2548

3397

4246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.111

Hom.:

2252

Bravo

AF:

0.129

Asia WGS

AF:

0.320

AC:

1107

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

1.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over