ENST00000518095.5:c.*631A>G

Variant names:

• chr5-163517402-A-G
• rs4869089
• ENST00000518095.5:c.*631A>G

Variant summary

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

The ENST00000518095.5(MAT2B):​c.*631A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 443,972 control chromosomes in the GnomAD database, including 50,661 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 0.40 (14019 hom., cov: 32)
  • Exomes 𝑓: 0.49 (36642 hom.)
• Consequence: MAT2B ENST00000518095.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503
• Publications: 2 publications found

Genes affected

MAT2B (HGNC:6905): (methionine adenosyltransferase 2 non-catalytic beta subunit) The protein encoded by this gene belongs to the methionine adenosyltransferase (MAT) family. MAT catalyzes the biosynthesis of S-adenosylmethionine from methionine and ATP. This protein is the regulatory beta subunit of MAT. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518095.5. 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
	MAT2B	NM_013283.5	MANE Select	c.721-159A>G		intron	N/A	NP_037415.1
	MAT2B	NM_182796.2		c.688-159A>G		intron	N/A	NP_877725.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT2B	ENST00000518095.5	TSL:1	c.*631A>G		3_prime_UTR	Exon 5 of 5	ENSP00000428046.1
	MAT2B	ENST00000321757.11	TSL:1 MANE Select	c.721-159A>G		intron	N/A	ENSP00000325425.6
	MAT2B	ENST00000280969.9	TSL:1	c.688-159A>G		intron	N/A	ENSP00000280969.5

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59647 AN: 150862 Hom.: 14016 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.430

GnomAD4 exome AF: 0.485 AC: 142200 AN: 292988 Hom.: 36642 Cov.: 3 AF XY: 0.487 AC XY: 74418 AN XY: 152900

African (AFR) AF: 0.134 AC: 1362 AN: 10154

American (AMR) AF: 0.549 AC: 7562 AN: 13780

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 4767 AN: 9462

East Asian (EAS) AF: 0.759 AC: 19563 AN: 25784

South Asian (SAS) AF: 0.473 AC: 8097 AN: 17110

European-Finnish (FIN) AF: 0.477 AC: 11709 AN: 24558

Middle Eastern (MID) AF: 0.467 AC: 607 AN: 1300

European-Non Finnish (NFE) AF: 0.464 AC: 80601 AN: 173588

Other (OTH) AF: 0.460 AC: 7932 AN: 17252

GnomAD4 genome AF: 0.395 AC: 59646 AN: 150984 Hom.: 14019 Cov.: 32 AF XY: 0.401 AC XY: 29578 AN XY: 73790

African (AFR) AF: 0.137 AC: 5601 AN: 40802

American (AMR) AF: 0.510 AC: 7752 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1770 AN: 3464

East Asian (EAS) AF: 0.759 AC: 3922 AN: 5166

South Asian (SAS) AF: 0.491 AC: 2346 AN: 4778

European-Finnish (FIN) AF: 0.480 AC: 4997 AN: 10412

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31836 AN: 67848

Other (OTH) AF: 0.425 AC: 893 AN: 2102

Alfa AF: 0.448 Hom.: 59981

Bravo AF: 0.384

Asia WGS AF: 0.523 AC: 1819 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.32
PhyloP100		-0.50
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: rs4869089; hg19: chr5-162944408;