rs10813960

Variant names:

• chr9-33180364-C-T
• rs10813960
• ENST00000654325.2:n.1353C>T

Variant summary

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

The ENST00000654325.2(B4GALT1-AS1):​n.1353C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,048 control chromosomes in the GnomAD database, including 5,077 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 0.24 (5077 hom., cov: 32)
• Consequence: B4GALT1-AS1 ENST00000654325.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251
• Publications: 17 publications found

Genes affected

B4GALT1-AS1 (HGNC:49910): (B4GALT1 antisense RNA 1)

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALT1	XM_047423231.1	c.-1008-2405G>A		intron_variant	Intron 1 of 8		XP_047279187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALT1-AS1	ENST00000654325.2	n.1353C>T		non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37024 AN: 151930 Hom.: 5078 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.258

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.244 AC: 37041 AN: 152048 Hom.: 5077 Cov.: 32 AF XY: 0.245 AC XY: 18193 AN XY: 74318

African (AFR) AF: 0.154 AC: 6378 AN: 41490

American (AMR) AF: 0.222 AC: 3391 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3472

East Asian (EAS) AF: 0.531 AC: 2745 AN: 5172

South Asian (SAS) AF: 0.339 AC: 1631 AN: 4818

European-Finnish (FIN) AF: 0.227 AC: 2399 AN: 10548

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18416 AN: 67970

Other (OTH) AF: 0.256 AC: 541 AN: 2114

Alfa AF: 0.251 Hom.: 7288

Bravo AF: 0.238

Asia WGS AF: 0.387 AC: 1342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.2
DANN	Benign	0.75
PhyloP100		-0.25

Splicing

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

Other links and lift over

dbSNP: rs10813960; hg19: chr9-33180362; COSMIC: COSV70211225;