Genetic Variant MAT2B:c.30+2049T>G (chr5-163505473-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000280969.9(MAT2B):c.30+2049T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00687 in 1,206,178 control chromosomes in the GnomAD database, including 429 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 0.034 ( 252 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 177 hom. )

Consequence

MAT2B
ENST00000280969.9 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.874

Publications

0 publications found

Variant links:

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]

MAT2B links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2B	NM_182796.2 link	c.30+2049T>G		intron_variant	Intron 1 of 6		NP_877725.1	Q9NZL9-2
MAT2B	NM_013283.5 link	c.-214T>G		upstream_gene_variant		ENST00000321757.11	NP_037415.1	Q9NZL9-1A0A140VJP2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT2B	ENST00000321757.11 link	c.-214T>G		upstream_gene_variant		1	NM_013283.5	ENSP00000325425.6		Q9NZL9-1

Frequencies

GnomAD3 genomes

AF:

0.0335

AC:

5104

AN:

152208

Hom.:

251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.0287

GnomAD4 exome

AF:

0.00301

AC:

3170

AN:

1053852

Hom.:

177

AF XY:

0.00267

AC XY:

1333

AN XY:

498408

show subpopulations

African (AFR)

AF:

0.116

AC:

2602

AN:

22382

American (AMR)

AF:

0.0114

AC:

AN:

8344

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14160

East Asian (EAS)

AF:

0.00

AC:

AN:

26344

South Asian (SAS)

AF:

0.0000551

AC:

AN:

18150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24684

Middle Eastern (MID)

AF:

0.00314

AC:

AN:

2870

European-Non Finnish (NFE)

AF:

0.000145

AC:

130

AN:

894248

Other (OTH)

AF:

0.00780

AC:

333

AN:

42670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

141

283

424

566

707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0336

AC:

5117

AN:

152326

Hom.:

252

Cov.:

AF XY:

0.0340

AC XY:

2534

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.115

AC:

4774

AN:

41570

American (AMR)

AF:

0.0165

AC:

253

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68024

Other (OTH)

AF:

0.0284

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

246

492

739

985

1231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0263

Hom.:

Bravo

AF:

0.0380

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.0

(source)

DANN

Benign

0.76

PhyloP100

-0.87

PromoterAI

0.036

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over