rs2291418

Positions:

• chr5-179798324-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014275.5(MGAT4B):​c.1510+23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 1,612,778 control chromosomes in the GnomAD database, including 1,034 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 0.033 (129 hom., cov: 33)
  • Exomes 𝑓: 0.033 (905 hom.)
• Consequence: MGAT4B NM_014275.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.741

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]

MIR1229 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0332 (5061/152264) while in subpopulation AFR AF= 0.0466 (1938/41562). AF 95% confidence interval is 0.0449. There are 129 homozygotes in gnomad4. There are 2323 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 129 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGAT4B	NM_014275.5	c.1510+23C>T		intron_variant		ENST00000292591.12	NP_055090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGAT4B	ENST00000292591.12	c.1510+23C>T		intron_variant		1	NM_014275.5	ENSP00000292591.7

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5061 AN: 152146 Hom.: 129 Cov.: 33

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.00659

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0347

Gnomad OTH AF: 0.0316

GnomAD3 exomes AF: 0.0262 AC: 6533 AN: 249748 Hom.: 110 AF XY: 0.0260 AC XY: 3529 AN XY: 135482

Gnomad AFR exome AF: 0.0495

Gnomad AMR exome AF: 0.0178

Gnomad ASJ exome AF: 0.0371

Gnomad EAS exome AF: 0.00131

Gnomad SAS exome AF: 0.0164

Gnomad FIN exome AF: 0.00930

Gnomad NFE exome AF: 0.0343

Gnomad OTH exome AF: 0.0270

GnomAD4 exome AF: 0.0326 AC: 47679 AN: 1460514 Hom.: 905 Cov.: 32 AF XY: 0.0324 AC XY: 23545 AN XY: 726562

Gnomad4 AFR exome AF: 0.0474

Gnomad4 AMR exome AF: 0.0179

Gnomad4 ASJ exome AF: 0.0389

Gnomad4 EAS exome AF: 0.00186

Gnomad4 SAS exome AF: 0.0166

Gnomad4 FIN exome AF: 0.0106

Gnomad4 NFE exome AF: 0.0359

Gnomad4 OTH exome AF: 0.0352

GnomAD4 genome AF: 0.0332 AC: 5061 AN: 152264 Hom.: 129 Cov.: 33 AF XY: 0.0312 AC XY: 2323 AN XY: 74458

Gnomad4 AFR AF: 0.0466

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.00659

Gnomad4 NFE AF: 0.0347

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.0354 Hom.: 44

Bravo AF: 0.0349

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.99
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2291418; hg19: chr5-179225324;