rs12515448

Variant names:

• chr5-163513041-G-A
• rs12515448
• NM_013283.5:c.259-514G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013283.5(MAT2B):​c.259-514G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 187,634 control chromosomes in the GnomAD database, including 18,594 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 (14239 hom., cov: 32)
  • Exomes 𝑓: 0.50 (4355 hom.)
• Consequence: MAT2B NM_013283.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2B	NM_013283.5	c.259-514G>A		intron_variant	Intron 2 of 6	ENST00000321757.11	NP_037415.1
MAT2B	NM_182796.2	c.226-514G>A		intron_variant	Intron 2 of 6		NP_877725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT2B	ENST00000321757.11	c.259-514G>A		intron_variant	Intron 2 of 6	1	NM_013283.5	ENSP00000325425.6

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60153 AN: 151916 Hom.: 14235 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.497 AC: 17685 AN: 35598 Hom.: 4355 Cov.: 0 AF XY: 0.495 AC XY: 9410 AN XY: 19020

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.572

Gnomad4 ASJ exome AF: 0.524

Gnomad4 EAS exome AF: 0.713

Gnomad4 SAS exome AF: 0.501

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.491

GnomAD4 genome AF: 0.396 AC: 60154 AN: 152036 Hom.: 14239 Cov.: 32 AF XY: 0.401 AC XY: 29796 AN XY: 74306

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.429

Alfa AF: 0.433 Hom.: 2107

Bravo AF: 0.388

Asia WGS AF: 0.523 AC: 1817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.091
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs12515448; hg19: chr5-162940047;