rs166624

chr5-179800286-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014275.5(MGAT4B):c.720-27C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,611,510 control chromosomes in the GnomAD database, including 26,414 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 0.23 (4591 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21823 hom.)
• Consequence: MGAT4B NM_014275.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980

Genes affected

MGAT4B (HGNC:7048): (alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B) This gene encodes a key glycosyltransferase that regulates the formation of tri- and multiantennary branching structures in the Golgi apparatus. The encoded protein, in addition to the related isoenzyme A, catalyzes the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc in a beta-1,4 linkage to the Man-alpha-1,3-Man-beta-1,4-GlcNAc arm of R-Man-alpha-1,6(GlcNAc-beta-1,2-Man-alpha-1,3)Man-beta-1,4-GlcNAc-beta-1,4-GlcNAc-beta-1-Asn. The encoded protein may play a role in regulating the availability of serum glycoproteins, oncogenesis, and differentiation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGAT4B	NM_014275.5	c.720-27C>A		intron_variant		ENST00000292591.12
MGAT4B	NM_054013.3	c.765-27C>A		intron_variant
MGAT4B	XM_024454349.2	c.285-27C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGAT4B	ENST00000292591.12	c.720-27C>A		intron_variant		1	NM_014275.5	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34333 AN: 151894 Hom.: 4591 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.218

GnomAD3 exomes AF: 0.180 AC: 44761 AN: 249240 Hom.: 4540 AF XY: 0.175 AC XY: 23611 AN XY: 135226

Gnomad AFR exome AF: 0.382

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.253

Gnomad SAS exome AF: 0.145

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.182

GnomAD4 exome AF: 0.167 AC: 243473 AN: 1459498 Hom.: 21823 Cov.: 34 AF XY: 0.166 AC XY: 120414 AN XY: 726144

Gnomad4 AFR exome AF: 0.385

Gnomad4 AMR exome AF: 0.173

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.270

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.226 AC: 34355 AN: 152012 Hom.: 4591 Cov.: 32 AF XY: 0.222 AC XY: 16497 AN XY: 74318

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.216

Alfa AF: 0.173 Hom.: 2757

Bravo AF: 0.239

Asia WGS AF: 0.194 AC: 671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.0
Dann	Benign	0.77

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: rs166624; hg19: chr5-179227286; COSMIC: COSV52978008; COSMIC: COSV52978008;