2-167782126-A-T

Variant names:

• chr2-167782126-A-T
• rs971257
• NM_020981.4:c.-351-36546A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020981.4(B3GALT1):​c.-351-36546A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,982 control chromosomes in the GnomAD database, including 21,930 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 0.53 (21930 hom., cov: 32)
• Consequence: B3GALT1 NM_020981.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32
• Publications: 2 publications found

Genes affected

B3GALT1 (HGNC:916): (beta-1,3-galactosyltransferase 1) This gene is a member of the beta-1,3-galactosyltransferase (beta3GalT) gene family. This family encodes type II membrane-bound glycoproteins with diverse enzymatic functions using different donor substrates (UDP-galactose and UDP-N-acetylglucosamine) and different acceptor sugars (N-acetylglucosamine, galactose, N-acetylgalactosamine). The beta3GalT genes are distantly related to the Drosophila Brainiac gene and have the protein coding sequence contained in a single exon. The beta3GalT proteins also contain conserved sequences not found in the beta4GalT or alpha3GalT proteins. The carbohydrate chains synthesized by these enzymes are designated as type 1, whereas beta4GalT enzymes synthesize type 2 carbohydrate chains. The ratio of type 1:type 2 chains changes during embryogenesis. By sequence similarity, the beta3GalT genes fall into at least two groups: beta3GalT4 and 4 other beta3GalT genes (beta3GalT1-3, beta3GalT5). This gene is expressed exclusively in the brain. The encoded protein shows strict donor substrate specificity for UDP-galactose. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALT1	NM_020981.4	c.-351-36546A>T		intron_variant	Intron 3 of 4	ENST00000392690.4	NP_066191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GALT1	ENST00000392690.4	c.-351-36546A>T		intron_variant	Intron 3 of 4	6	NM_020981.4	ENSP00000376456.2

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80471 AN: 151862 Hom.: 21898 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.530 AC: 80564 AN: 151982 Hom.: 21930 Cov.: 32 AF XY: 0.532 AC XY: 39510 AN XY: 74298

African (AFR) AF: 0.633 AC: 26223 AN: 41440

American (AMR) AF: 0.481 AC: 7354 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1874 AN: 3470

East Asian (EAS) AF: 0.765 AC: 3938 AN: 5146

South Asian (SAS) AF: 0.484 AC: 2329 AN: 4812

European-Finnish (FIN) AF: 0.542 AC: 5731 AN: 10568

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31416 AN: 67956

Other (OTH) AF: 0.515 AC: 1086 AN: 2110

Alfa AF: 0.491 Hom.: 2357

Bravo AF: 0.532

Asia WGS AF: 0.572 AC: 1989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.5
DANN	Benign	0.83
PhyloP100		2.3

Splicing

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

Other links and lift over

dbSNP: rs971257; hg19: chr2-168638636;