9-33111276-AAACAAC-AAAC

Variant names:

• chr9-33111276-AAAC-A
• rs754771244
• NM_001497.4:c.*2175_*2177delGTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001497.4(B4GALT1):​c.*2175_*2177delGTT 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, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.0720
• Publications: 0 publications found

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]

B4GALT1 Gene-Disease associations (from GenCC):

• B4GALT1-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001497.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALT1	NM_001497.4	MANE Select	c.*2175_*2177delGTT		3_prime_UTR	Exon 6 of 6	NP_001488.2
	B4GALT1	NM_001378495.1		c.*2175_*2177delGTT		3_prime_UTR	Exon 6 of 6	NP_001365424.1	P15291-2
	B4GALT1	NM_001378496.1		c.*2175_*2177delGTT		3_prime_UTR	Exon 5 of 5	NP_001365425.1	W6MEN3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALT1	ENST00000379731.5	TSL:1 MANE Select	c.*2175_*2177delGTT		3_prime_UTR	Exon 6 of 6	ENSP00000369055.4	P15291-1
	B4GALT1	ENST00000535206.6	TSL:1	c.649-6498_649-6496delGTT		intron	N/A	ENSP00000440341.1	Q86XA6
	B4GALT1	ENST00000860372.1		c.*2175_*2177delGTT		3_prime_UTR	Exon 7 of 7	ENSP00000530431.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 388

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.0520 AC: 1542 AN: 29636

American (AMR) AF: 0.0380 AC: 361 AN: 9504

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 140 AN: 2504

East Asian (EAS) AF: 0.203 AC: 490 AN: 2416

South Asian (SAS) AF: 0.122 AC: 320 AN: 2626

European-Finnish (FIN) AF: 0.0139 AC: 95 AN: 6846

Middle Eastern (MID) AF: 0.0146 AC: 3 AN: 206

European-Non Finnish (NFE) AF: 0.0501 AC: 2443 AN: 48726

Other (OTH) AF: 0.0447 AC: 63 AN: 1410

Alfa AF: 0.0536 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Congenital disorder of glycosylation (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.072
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs754771244; hg19: chr9-33111274;