9-33111563-GA-G

Position:

• chr9-33111563-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001497.4(B4GALT1):​c.*1890del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0326 in 152,730 control chromosomes in the GnomAD database, including 153 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (153 hom., cov: 32)
  • Exomes 𝑓: 0.0090 (0 hom.)
• Consequence: B4GALT1 NM_001497.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.208

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 -10 ACMG points.

• BP6: Variant 9-33111563-GA-G is Benign according to our data. Variant chr9-33111563-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 366619.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALT1	NM_001497.4	c.*1890del		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	c.*1890del		3_prime_UTR_variant	6/6	1	NM_001497.4	ENSP00000369055	P1
B4GALT1	ENST00000535206.5	c.649-6783del		intron_variant		1		ENSP00000440341

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4945 AN: 152170 Hom.: 150 Cov.: 32

Gnomad AFR AF: 0.0615

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0456

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00725

Gnomad OTH AF: 0.0320

GnomAD4 exome AF: 0.00905 AC: 4 AN: 442 Hom.: 0 Cov.: 0 AF XY: 0.00376 AC XY: 1 AN XY: 266

Gnomad4 FIN exome AF: 0.00939

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0327 AC: 4975 AN: 152288 Hom.: 153 Cov.: 32 AF XY: 0.0343 AC XY: 2551 AN XY: 74472

Gnomad4 AFR AF: 0.0618

Gnomad4 AMR AF: 0.0457

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.0182

Gnomad4 NFE AF: 0.00725

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0241 Hom.: 7

Bravo AF: 0.0373

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital disorder of glycosylation Benign:1

Likely benign, 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: rs3841451; hg19: chr9-33111561;