9-33104213-C-T

Variant names:

• chr9-33104213-C-T
• rs1556253
• ENST00000535206.6:c.*539G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378497.1(B4GALT1):​c.*539G>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 0.449 in 152,536 control chromosomes in the GnomAD database, including 17,846 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (17774 hom., cov: 31)
  • Exomes 𝑓: 0.46 (72 hom.)
• Consequence: B4GALT1 NM_001378497.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 3 publications found

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: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378497.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALT1	NM_001378497.1		c.*539G>A		3_prime_UTR	Exon 3 of 3	NP_001365426.1	Q86XA6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALT1	ENST00000535206.6	TSL:1	c.*539G>A		3_prime_UTR	Exon 3 of 3	ENSP00000440341.1	Q86XA6

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68177 AN: 151858 Hom.: 17767 Cov.: 31

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.494

GnomAD4 exome AF: 0.459 AC: 257 AN: 560 Hom.: 72 Cov.: 0 AF XY: 0.463 AC XY: 163 AN XY: 352

African (AFR) AF: 0.00 AC: 0 AN: 14

American (AMR) AF: 0.559 AC: 19 AN: 34

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 4 AN: 6

East Asian (EAS) AF: 0.300 AC: 3 AN: 10

South Asian (SAS) AF: 0.464 AC: 13 AN: 28

European-Finnish (FIN) AF: 0.188 AC: 3 AN: 16

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.481 AC: 202 AN: 420

Other (OTH) AF: 0.400 AC: 12 AN: 30

GnomAD4 genome AF: 0.449 AC: 68206 AN: 151976 Hom.: 17774 Cov.: 31 AF XY: 0.449 AC XY: 33332 AN XY: 74290

African (AFR) AF: 0.166 AC: 6899 AN: 41462

American (AMR) AF: 0.502 AC: 7666 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1913 AN: 3468

East Asian (EAS) AF: 0.381 AC: 1971 AN: 5178

South Asian (SAS) AF: 0.595 AC: 2862 AN: 4812

European-Finnish (FIN) AF: 0.572 AC: 6035 AN: 10552

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39194 AN: 67918

Other (OTH) AF: 0.496 AC: 1047 AN: 2110

Alfa AF: 0.403 Hom.: 5737

Bravo AF: 0.433

Asia WGS AF: 0.462 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1556253; hg19: chr9-33104211;