rs2291418

Variant names:

• chr5-179798324-G-A
• rs2291418
• NM_014275.5:c.1510+23C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 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]

MIR1229 (HGNC:33924): (microRNA 1229) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 129 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGAT4B	NM_014275.5	c.1510+23C>T		intron_variant	Intron 13 of 14	ENST00000292591.12	NP_055090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGAT4B	ENST00000292591.12	c.1510+23C>T		intron_variant	Intron 13 of 14	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

GnomAD2 exomes AF: 0.0262 AC: 6533 AN: 249748 AF XY: 0.0260

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 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

African (AFR) AF: 0.0474 AC: 1587 AN: 33466

American (AMR) AF: 0.0179 AC: 802 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 1017 AN: 26132

East Asian (EAS) AF: 0.00186 AC: 74 AN: 39696

South Asian (SAS) AF: 0.0166 AC: 1436 AN: 86250

European-Finnish (FIN) AF: 0.0106 AC: 552 AN: 52308

Middle Eastern (MID) AF: 0.0387 AC: 223 AN: 5768

European-Non Finnish (NFE) AF: 0.0359 AC: 39863 AN: 1111808

Other (OTH) AF: 0.0352 AC: 2125 AN: 60372

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

African (AFR) AF: 0.0466 AC: 1938 AN: 41562

American (AMR) AF: 0.0234 AC: 358 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3472

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5166

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4832

European-Finnish (FIN) AF: 0.00659 AC: 70 AN: 10622

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0347 AC: 2360 AN: 67988

Other (OTH) AF: 0.0313 AC: 66 AN: 2110

Alfa AF: 0.0356 Hom.: 46

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
PhyloP100		-0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2291418; hg19: chr5-179225324;