5-179800286-G-T

Variant names:

• chr5-179800286-G-T
• rs166624
• NM_014275.5:c.720-27C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014275.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT4B	NM_014275.5	MANE Select	c.720-27C>A		intron	N/A	NP_055090.1
	MGAT4B	NM_054013.3		c.765-27C>A		intron	N/A	NP_463459.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT4B	ENST00000292591.12	TSL:1 MANE Select	c.720-27C>A		intron	N/A	ENSP00000292591.7
	MGAT4B	ENST00000519836.5	TSL:1	c.561-27C>A		intron	N/A	ENSP00000430721.1
	MGAT4B	ENST00000518778.5	TSL:1	c.195-27C>A		intron	N/A	ENSP00000428906.1

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

GnomAD2 exomes AF: 0.180 AC: 44761 AN: 249240 AF XY: 0.175

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 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

African (AFR) AF: 0.385 AC: 12895 AN: 33472

American (AMR) AF: 0.173 AC: 7733 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4991 AN: 26126

East Asian (EAS) AF: 0.270 AC: 10706 AN: 39690

South Asian (SAS) AF: 0.145 AC: 12467 AN: 86204

European-Finnish (FIN) AF: 0.148 AC: 7750 AN: 52346

Middle Eastern (MID) AF: 0.221 AC: 1271 AN: 5762

European-Non Finnish (NFE) AF: 0.157 AC: 174651 AN: 1110828

Other (OTH) AF: 0.182 AC: 11009 AN: 60348

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

African (AFR) AF: 0.379 AC: 15676 AN: 41416

American (AMR) AF: 0.195 AC: 2985 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 712 AN: 3470

East Asian (EAS) AF: 0.237 AC: 1220 AN: 5150

South Asian (SAS) AF: 0.154 AC: 741 AN: 4820

European-Finnish (FIN) AF: 0.152 AC: 1609 AN: 10590

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10629 AN: 67972

Other (OTH) AF: 0.216 AC: 456 AN: 2114

Alfa AF: 0.176 Hom.: 3396

Bravo AF: 0.239

Asia WGS AF: 0.194 AC: 671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.0
DANN	Benign	0.77
PhyloP100		0.098
PromoterAI		0.0044	Neutral
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: rs166624; hg19: chr5-179227286; COSMIC: COSV52978008; COSMIC: COSV52978008;