NM_003780.5:c.*622C>T

Variant names:

• chr1-43991070-C-T
• rs7555
• NM_003780.5:c.*622C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003780.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALT2	NM_003780.5	MANE Select	c.*622C>T		3_prime_UTR	Exon 7 of 7	NP_003771.1
	B4GALT2	NM_030587.3		c.*622C>T		3_prime_UTR	Exon 7 of 7	NP_085076.2
	B4GALT2	NM_001005417.2		c.*622C>T		3_prime_UTR	Exon 7 of 7	NP_001005417.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALT2	ENST00000372324.6	TSL:1 MANE Select	c.*622C>T		3_prime_UTR	Exon 7 of 7	ENSP00000361399.1
	B4GALT2	ENST00000434555.7	TSL:1	c.*622C>T		3_prime_UTR	Exon 7 of 7	ENSP00000407468.3
	B4GALT2	ENST00000309519.8	TSL:2	c.*622C>T		3_prime_UTR	Exon 7 of 7	ENSP00000310696.7

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

African (AFR) AF: 0.194 AC: 14 AN: 72

American (AMR) AF: 0.122 AC: 139 AN: 1136

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 1 AN: 56

East Asian (EAS) AF: 0.167 AC: 6 AN: 36

South Asian (SAS) AF: 0.0746 AC: 47 AN: 630

European-Finnish (FIN) AF: 0.101 AC: 50 AN: 496

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0588 AC: 166 AN: 2824

Other (OTH) AF: 0.0691 AC: 13 AN: 188

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

African (AFR) AF: 0.257 AC: 10630 AN: 41438

American (AMR) AF: 0.125 AC: 1910 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0697 AC: 242 AN: 3472

East Asian (EAS) AF: 0.160 AC: 827 AN: 5162

South Asian (SAS) AF: 0.0956 AC: 460 AN: 4810

European-Finnish (FIN) AF: 0.125 AC: 1328 AN: 10598

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.0671 AC: 4563 AN: 67984

Other (OTH) AF: 0.119 AC: 252 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.87
PhyloP100		2.6
Mutation Taster		=100/0	polymorphism (auto)

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