9-33113324-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.09

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 -14 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 id is 1289695.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B4GALT1	NM_001497.4	c.*130G>A		3_prime_UTR_variant	6/6	ENST00000379731.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B4GALT1	ENST00000379731.5	c.*130G>A		3_prime_UTR_variant	6/6	1	NM_001497.4	P1
B4GALT1	ENST00000535206.5	c.649-8543G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20485 AN: 152076 Hom.: 1822 Cov.: 33

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.: 18 AF XY: 0.129 AC XY: 80804 AN XY: 628538

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.0539

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.452

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.135 AC: 20492 AN: 152194 Hom.: 1821 Cov.: 33 AF XY: 0.140 AC XY: 10416 AN XY: 74428

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0846

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.118

Alfa AF: 0.108 Hom.: 1385

Bravo AF: 0.129

Asia WGS AF: 0.320 AC: 1107 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	14
Dann	Benign	0.90

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: rs7019909; hg19: chr9-33113322; COSMIC: COSV65707404;