1-43991070-C-T

Position:

• chr1-43991070-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003780.5(B4GALT2):​c.*622C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 157,512 control chromosomes in the GnomAD database, including 1,920 homozygotes. 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: 𝑓 0.13 (1892 hom., cov: 32)
  • Exomes 𝑓: 0.080 (28 hom.)
• Consequence: B4GALT2 NM_003780.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62

Genes affected

B4GALT2 (HGNC:925): (beta-1,4-galactosyltransferase 2) 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. The enzyme encoded by this gene synthesizes N-acetyllactosamine in glycolipids and glycoproteins. Its substrate specificity is affected by alpha-lactalbumin but it is not expressed in lactating mammary tissue. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALT2	NM_003780.5	c.*622C>T		3_prime_UTR_variant	7/7	ENST00000372324.6	NP_003771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B4GALT2	ENST00000372324.6	c.*622C>T		3_prime_UTR_variant	7/7	1	NM_003780.5	ENSP00000361399.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20265 AN: 151956 Hom.: 1888 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0951

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0802 AC: 436 AN: 5438 Hom.: 28 Cov.: 0 AF XY: 0.0854 AC XY: 249 AN XY: 2916

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.122

Gnomad4 ASJ exome AF: 0.0179

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.0746

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.0588

Gnomad4 OTH exome AF: 0.0691

GnomAD4 genome AF: 0.133 AC: 20296 AN: 152074 Hom.: 1892 Cov.: 32 AF XY: 0.135 AC XY: 10015 AN XY: 74356

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.0697

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.0956

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0671

Gnomad4 OTH AF: 0.119

Alfa AF: 0.122 Hom.: 330

Bravo AF: 0.140

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.87

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: rs7555; hg19: chr1-44456742; COSMIC: COSV58843543; COSMIC: COSV58843543;