9-33167204-C-T

Variant names:

• chr9-33167204-C-T
• rs1166514148
• NM_001497.4:c.-35G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001497.4(B4GALT1):​c.-35G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: B4GALT1 NM_001497.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• 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-AS1 (HGNC:49910): (B4GALT1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).

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.-35G>A		5_prime_UTR	Exon 1 of 6	NP_001488.2
	B4GALT1	NM_001378496.1		c.-35G>A		5_prime_UTR	Exon 1 of 5	NP_001365425.1	W6MEN3
	B4GALT1	NM_001378497.1		c.-35G>A		5_prime_UTR	Exon 1 of 3	NP_001365426.1	Q86XA6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALT1	ENST00000379731.5	TSL:1 MANE Select	c.-35G>A		5_prime_UTR	Exon 1 of 6	ENSP00000369055.4	P15291-1
	B4GALT1	ENST00000535206.6	TSL:1	c.-35G>A		5_prime_UTR	Exon 1 of 3	ENSP00000440341.1	Q86XA6
	B4GALT1	ENST00000860372.1		c.-35G>A		5_prime_UTR	Exon 1 of 7	ENSP00000530431.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000613 AC: 1 AN: 163222 AF XY: 0.0000109

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000141

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399146 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 691762

African (AFR) AF: 0.00 AC: 0 AN: 30282

American (AMR) AF: 0.00 AC: 0 AN: 36402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23398

East Asian (EAS) AF: 0.00 AC: 0 AN: 37352

South Asian (SAS) AF: 0.00 AC: 0 AN: 79150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4258

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085122

Other (OTH) AF: 0.00 AC: 0 AN: 57476

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.95
PhyloP100		0.032
PromoterAI		0.091	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1166514148; hg19: chr9-33167202;