rs754771244

Variant names:

• chr9-33111276-AAACAAC-A
• rs754771244
• NM_001497.4:c.*2172_*2177delGTTGTT

Your query was ambiguous. Multiple possible variants found:

• chr9-33111276-AAACAAC-A
• chr9-33111276-AAACAAC-AAAC
• chr9-33111276-AAACAAC-AAACAACAAC
• chr9-33111276-AAACAAC-AAACAACAACAAC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001497.4(B4GALT1):​c.*2172_*2177delGTTGTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000095 (0 hom., cov: 6)
  • Failed GnomAD Quality Control
• Consequence: B4GALT1 NM_001497.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.*2172_*2177delGTTGTT		3_prime_UTR	Exon 6 of 6	NP_001488.2
	B4GALT1	NM_001378495.1		c.*2172_*2177delGTTGTT		3_prime_UTR	Exon 6 of 6	NP_001365424.1	P15291-2
	B4GALT1	NM_001378496.1		c.*2172_*2177delGTTGTT		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.*2172_*2177delGTTGTT		3_prime_UTR	Exon 6 of 6	ENSP00000369055.4	P15291-1
	B4GALT1	ENST00000535206.6	TSL:1	c.649-6501_649-6496delGTTGTT		intron	N/A	ENSP00000440341.1	Q86XA6
	B4GALT1	ENST00000860372.1		c.*2172_*2177delGTTGTT		3_prime_UTR	Exon 7 of 7	ENSP00000530431.1

Frequencies

GnomAD3 genomes AF: 0.00000947 AC: 1 AN: 105542 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.0000335

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000947 AC: 1 AN: 105542 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 50650

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000335 AC: 1 AN: 29844

American (AMR) AF: 0.00 AC: 0 AN: 9568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2530

East Asian (EAS) AF: 0.00 AC: 0 AN: 2484

South Asian (SAS) AF: 0.00 AC: 0 AN: 2668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 224

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 49222

Other (OTH) AF: 0.00 AC: 0 AN: 1414

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.072

Splicing

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

Other links and lift over

dbSNP: rs754771244; hg19: chr9-33111274;