9-33111276-AAAC-A

Position:

• chr9-33111276-AAAC-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001497.4(B4GALT1):​c.*2175_*2177del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.052 (353 hom., cov: 6)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: B4GALT1 NM_001497.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0720

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B4GALT1	NM_001497.4	c.*2175_*2177del		3_prime_UTR_variant	6/6	ENST00000379731.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B4GALT1	ENST00000379731.5	c.*2175_*2177del		3_prime_UTR_variant	6/6	1	NM_001497.4	P1
B4GALT1	ENST00000535206.5	c.649-6498_649-6496del		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0524 AC: 5475 AN: 104508 Hom.: 354 Cov.: 6

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.0222

Gnomad AMR AF: 0.0380

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.0180

Gnomad NFE AF: 0.0501

Gnomad OTH AF: 0.0443

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 396 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 244

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0523 AC: 5473 AN: 104596 Hom.: 353 Cov.: 6 AF XY: 0.0511 AC XY: 2568 AN XY: 50260

Gnomad4 AFR AF: 0.0520

Gnomad4 AMR AF: 0.0380

Gnomad4 ASJ AF: 0.0559

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0139

Gnomad4 NFE AF: 0.0501

Gnomad4 OTH AF: 0.0447

Alfa AF: 0.0536 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital disorder of glycosylation Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs754771244; hg19: chr9-33111274;