rs6512586

Variant names:

• chr20-49684609-G-A
• rs6512586
• NM_004776.4:c.116-27907C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-49684609-G-A
• chr20-49684609-G-C

Variant summary

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

The NM_004776.4(B4GALT5):​c.116-27907C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 517,860 control chromosomes in the GnomAD database, including 73,488 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 0.49 (18689 hom., cov: 32)
  • Exomes 𝑓: 0.54 (54799 hom.)
• Consequence: B4GALT5 NM_004776.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989
• Publications: 9 publications found

Genes affected

B4GALT5 (HGNC:928): (beta-1,4-galactosyltransferase 5) 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 function of the enzyme encoded by this gene is not clear. This gene was previously designated as B4GALT4 but was renamed to B4GALT5. In the literature it is also referred to as beta4GalT2. [provided by RefSeq, Jul 2008]

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 (SAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALT5	NM_004776.4	c.116-27907C>T		intron_variant	Intron 1 of 8	ENST00000371711.4	NP_004767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALT5	ENST00000371711.4	c.116-27907C>T		intron_variant	Intron 1 of 8	1	NM_004776.4	ENSP00000360776.4

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74350 AN: 151690 Hom.: 18677 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.497

GnomAD2 exomes AF: 0.518 AC: 118033 AN: 227938 AF XY: 0.533

Gnomad AFR exome AF: 0.375

Gnomad AMR exome AF: 0.448

Gnomad ASJ exome AF: 0.522

Gnomad EAS exome AF: 0.370

Gnomad FIN exome AF: 0.504

Gnomad NFE exome AF: 0.546

Gnomad OTH exome AF: 0.529

GnomAD4 exome AF: 0.541 AC: 198006 AN: 366052 Hom.: 54799 Cov.: 0 AF XY: 0.555 AC XY: 116397 AN XY: 209876

African (AFR) AF: 0.375 AC: 3941 AN: 10508

American (AMR) AF: 0.450 AC: 16320 AN: 36288

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 6146 AN: 11734

East Asian (EAS) AF: 0.377 AC: 4956 AN: 13148

South Asian (SAS) AF: 0.652 AC: 43461 AN: 66680

European-Finnish (FIN) AF: 0.506 AC: 8497 AN: 16780

Middle Eastern (MID) AF: 0.610 AC: 1739 AN: 2852

European-Non Finnish (NFE) AF: 0.543 AC: 103969 AN: 191468

Other (OTH) AF: 0.541 AC: 8977 AN: 16594

GnomAD4 genome AF: 0.490 AC: 74395 AN: 151808 Hom.: 18689 Cov.: 32 AF XY: 0.490 AC XY: 36346 AN XY: 74192

African (AFR) AF: 0.387 AC: 16046 AN: 41424

American (AMR) AF: 0.467 AC: 7122 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1854 AN: 3472

East Asian (EAS) AF: 0.388 AC: 2007 AN: 5176

South Asian (SAS) AF: 0.652 AC: 3146 AN: 4828

European-Finnish (FIN) AF: 0.503 AC: 5283 AN: 10508

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.549 AC: 37210 AN: 67824

Other (OTH) AF: 0.499 AC: 1052 AN: 2108

Alfa AF: 0.527 Hom.: 77017

Bravo AF: 0.481

Asia WGS AF: 0.570 AC: 1981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.49
DANN	Benign	0.67
PhyloP100		-0.99
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: rs6512586; hg19: chr20-48301146; COSMIC: COSV65493865;