3-161102736-G-C

Position:

• chr3-161102736-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GALNT1	NM_003781.4	c.-130+691C>G		intron_variant		ENST00000320474.10	NP_003772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GALNT1	ENST00000320474.10	c.-130+691C>G		intron_variant		1	NM_003781.4	ENSP00000323479	P1

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

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.471

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.63

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: rs4557202; hg19: chr3-160820524;