9-33167270-G-A

Position:

• chr9-33167270-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001497.4(B4GALT1):​c.-101C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00949 in 1,378,798 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0090 (14 hom., cov: 33)
  • Exomes 𝑓: 0.0095 (83 hom.)
• Consequence: B4GALT1 NM_001497.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00100

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:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 9-33167270-G-A is Benign according to our data. Variant chr9-33167270-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1326049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALT1	NM_001497.4	c.-101C>T		5_prime_UTR_variant	1/6	ENST00000379731.5	NP_001488.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B4GALT1	ENST00000379731.5	c.-101C>T		5_prime_UTR_variant	1/6	1	NM_001497.4	ENSP00000369055.4
B4GALT1	ENST00000535206.5	c.-101C>T		5_prime_UTR_variant	1/3	1		ENSP00000440341.1
B4GALT1-AS1	ENST00000426270.5	n.72+224G>A		intron_variant		2
B4GALT1-AS1	ENST00000654325.1	n.99+224G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00904 AC: 1375 AN: 152162 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00558

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.00954 AC: 11707 AN: 1226524 Hom.: 83 Cov.: 23 AF XY: 0.00947 AC XY: 5646 AN XY: 596334

Gnomad4 AFR exome AF: 0.00106

Gnomad4 AMR exome AF: 0.00242

Gnomad4 ASJ exome AF: 0.00549

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00668

Gnomad4 FIN exome AF: 0.0315

Gnomad4 NFE exome AF: 0.00972

Gnomad4 OTH exome AF: 0.00918

GnomAD4 genome AF: 0.00903 AC: 1375 AN: 152274 Hom.: 14 Cov.: 33 AF XY: 0.00968 AC XY: 721 AN XY: 74448

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.0299

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.0139 Hom.: 1

Bravo AF: 0.00660

Asia WGS AF: 0.00637 AC: 22 AN: 3466

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs184789571; hg19: chr9-33167268;