chr9-33113198-G-T

Position:

• chr9-33113198-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001497.4(B4GALT1):​c.*256C>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 0.944 in 541,368 control chromosomes in the GnomAD database, including 241,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (65881 hom., cov: 32)
  • Exomes 𝑓: 0.95 (175475 hom.)
• Consequence: B4GALT1 NM_001497.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.829

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 9-33113198-G-T is Benign according to our data. Variant chr9-33113198-G-T is described in ClinVar as [Benign]. Clinvar id is 1238534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALT1	NM_001497.4	c.*256C>A		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.*256C>A		3_prime_UTR_variant	6/6	1	NM_001497.4	ENSP00000369055	P1
B4GALT1	ENST00000535206.5	c.649-8417C>A		intron_variant		1		ENSP00000440341

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141460 AN: 152140 Hom.: 65835 Cov.: 32

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.945

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.984

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.930

GnomAD4 exome AF: 0.949 AC: 369403 AN: 389110 Hom.: 175475 Cov.: 4 AF XY: 0.951 AC XY: 196568 AN XY: 206680

Gnomad4 AFR exome AF: 0.878

Gnomad4 AMR exome AF: 0.958

Gnomad4 ASJ exome AF: 0.945

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.979

Gnomad4 FIN exome AF: 0.974

Gnomad4 NFE exome AF: 0.939

Gnomad4 OTH exome AF: 0.943

GnomAD4 genome AF: 0.930 AC: 141564 AN: 152258 Hom.: 65881 Cov.: 32 AF XY: 0.933 AC XY: 69469 AN XY: 74444

Gnomad4 AFR AF: 0.880

Gnomad4 AMR AF: 0.945

Gnomad4 ASJ AF: 0.947

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.985

Gnomad4 FIN AF: 0.979

Gnomad4 NFE AF: 0.938

Gnomad4 OTH AF: 0.930

Alfa AF: 0.936 Hom.: 66966

Bravo AF: 0.925

Asia WGS AF: 0.986 AC: 3428 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.86

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: rs7019896; hg19: chr9-33113196;