chr18-31693166-A-G

Position:

• chr18-31693166-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALT6	XM_005258387.5	c.80-26794T>C		intron_variant			XP_005258444.1
		n.31693166A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

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

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.0953

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0243

Gnomad4 SAS AF: 0.0416

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.130

Alfa AF: 0.132 Hom.: 2973

Bravo AF: 0.139

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10438933; hg19: chr18-29273129;