3-161102736-G-C

Variant names:

• chr3-161102736-G-C
• rs4557202
• NM_003781.4:c.-130+691C>G

Variant summary

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

The NM_003781.4(B3GALNT1):​c.-130+691C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,876 control chromosomes in the GnomAD database, including 17,984 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 0.48 (17984 hom., cov: 31)
• Consequence: B3GALNT1 NM_003781.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348
• Publications: 13 publications found

Genes affected

B3GALNT1 (HGNC:918): (beta-1,3-N-acetylgalactosaminyltransferase 1 (Globoside blood group)) 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). The encoded protein of this gene does not use N-acetylglucosamine as an acceptor sugar at all. [provided by RefSeq, Mar 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003781.4. 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
	B3GALNT1	NM_003781.4	MANE Select	c.-130+691C>G		intron	N/A	NP_003772.1
	B3GALNT1	NM_001349162.2		c.112+691C>G		intron	N/A	NP_001336091.1
	B3GALNT1	NM_001349163.2		c.112+691C>G		intron	N/A	NP_001336092.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALNT1	ENST00000320474.10	TSL:1 MANE Select	c.-130+691C>G		intron	N/A	ENSP00000323479.4
	B3GALNT1	ENST00000392781.7	TSL:1	c.-249+377C>G		intron	N/A	ENSP00000376532.2
	B3GALNT1	ENST00000488170.5	TSL:1	c.-130+691C>G		intron	N/A	ENSP00000420163.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73193 AN: 151758 Hom.: 17955 Cov.: 31

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.482 AC: 73269 AN: 151876 Hom.: 17984 Cov.: 31 AF XY: 0.485 AC XY: 36034 AN XY: 74236

African (AFR) AF: 0.426 AC: 17639 AN: 41410

American (AMR) AF: 0.517 AC: 7899 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1841 AN: 3470

East Asian (EAS) AF: 0.808 AC: 4152 AN: 5140

South Asian (SAS) AF: 0.576 AC: 2779 AN: 4822

European-Finnish (FIN) AF: 0.477 AC: 5025 AN: 10540

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.476 AC: 32325 AN: 67928

Other (OTH) AF: 0.471 AC: 992 AN: 2106

Alfa AF: 0.470 Hom.: 2333

Bravo AF: 0.482

Asia WGS AF: 0.659 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		0.35
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: rs4557202; hg19: chr3-160820524;