rs12695382

Variant names:

• chr3-119229324-A-G
• rs12695382
• NM_003778.4:c.253+523T>C

Variant summary

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

The NM_003778.4(B4GALT4):​c.253+523T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,276 control chromosomes in the GnomAD database, including 1,025 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 0.11 (1025 hom., cov: 33)
• Consequence: B4GALT4 NM_003778.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.724
• Publications: 11 publications found

Genes affected

B4GALT4 (HGNC:927): (beta-1,4-galactosyltransferase 4) This gene is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes. 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. By sequence similarity, the beta4GalTs form four groups: beta4GalT1 and beta4GalT2, beta4GalT3 and beta4GalT4, beta4GalT5 and beta4GalT6, and beta4GalT7. The enzyme encoded by this gene appears to mainly play a role in glycolipid biosynthesis. Two alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

B4GALT4-AS1 (HGNC:40090): (B4GALT4 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003778.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALT4	NM_003778.4	MANE Select	c.253+523T>C		intron	N/A	NP_003769.1	B2RAZ5
	B4GALT4	NM_212543.2		c.253+523T>C		intron	N/A	NP_997708.1	O60513
	B4GALT4-AS1	NR_046574.1		n.197-821A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALT4	ENST00000393765.7	TSL:1 MANE Select	c.253+523T>C		intron	N/A	ENSP00000377360.2	O60513
	B4GALT4	ENST00000483209.5	TSL:1	c.253+523T>C		intron	N/A	ENSP00000420161.1	O60513
	B4GALT4	ENST00000467604.5	TSL:1	c.253+523T>C		intron	N/A	ENSP00000417226.1	C9J3R8

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16500 AN: 152156 Hom.: 1021 Cov.: 33

Gnomad AFR AF: 0.0606

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0930

Gnomad ASJ AF: 0.0943

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0940

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0937

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

GnomAD4 genome AF: 0.108 AC: 16511 AN: 152276 Hom.: 1025 Cov.: 33 AF XY: 0.108 AC XY: 8020 AN XY: 74440

African (AFR) AF: 0.0605 AC: 2517 AN: 41570

American (AMR) AF: 0.0929 AC: 1421 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0943 AC: 327 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1249 AN: 5174

South Asian (SAS) AF: 0.131 AC: 632 AN: 4822

European-Finnish (FIN) AF: 0.0940 AC: 998 AN: 10618

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9073 AN: 68010

Other (OTH) AF: 0.0979 AC: 207 AN: 2114

Alfa AF: 0.116 Hom.: 193

Bravo AF: 0.105

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	9.3
DANN	Benign	0.29
PhyloP100		0.72
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: rs12695382; hg19: chr3-118948171;