rs10438933

Variant names:

• chr18-31693166-A-G
• rs10438933
• XM_005258387.5:c.80-26794T>C

Variant summary

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

The XM_005258387.5(B4GALT6):​c.80-26794T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,276 control chromosomes in the GnomAD database, including 1,566 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 0.14 (1566 hom., cov: 32)
• Consequence: B4GALT6 XM_005258387.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 12 publications found

Genes affected

B4GALT6 (HGNC:929): (beta-1,4-galactosyltransferase 6) This gene is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes in human. 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. This gene produces multiple protein isoforms - some of which are predicted to lack the N-terminal hydrophobic signal sequence and transmembrane domain. By sequence similarity, the beta4GalTs form four groups: beta4GalT1 and beta4GalT2, beta4GalT3 and beta4GalT4, beta4GalT5 and beta4GalT6, and beta4GalT7. The canonical enzyme encoded by this gene is a lactosylceramide synthase important for glycolipid biosynthesis. [provided by RefSeq, Jan 2020]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20901 AN: 152158 Hom.: 1564 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0242

Gnomad SAS AF: 0.0418

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.137 AC: 20901 AN: 152276 Hom.: 1566 Cov.: 32 AF XY: 0.136 AC XY: 10130 AN XY: 74454

African (AFR) AF: 0.185 AC: 7668 AN: 41526

American (AMR) AF: 0.0953 AC: 1459 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3472

East Asian (EAS) AF: 0.0243 AC: 126 AN: 5186

South Asian (SAS) AF: 0.0416 AC: 201 AN: 4834

European-Finnish (FIN) AF: 0.140 AC: 1482 AN: 10610

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8958 AN: 68026

Other (OTH) AF: 0.130 AC: 275 AN: 2114

Alfa AF: 0.132 Hom.: 4013

Bravo AF: 0.139

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.45
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs10438933; hg19: chr18-29273129;