rs12515448

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-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

African (AFR) AF: 0.131 AC: 28 AN: 214

American (AMR) AF: 0.572 AC: 1579 AN: 2762

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 311 AN: 594

East Asian (EAS) AF: 0.713 AC: 479 AN: 672

South Asian (SAS) AF: 0.501 AC: 3255 AN: 6492

European-Finnish (FIN) AF: 0.489 AC: 788 AN: 1610

Middle Eastern (MID) AF: 0.466 AC: 55 AN: 118

European-Non Finnish (NFE) AF: 0.483 AC: 10273 AN: 21270

Other (OTH) AF: 0.491 AC: 917 AN: 1866

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

African (AFR) AF: 0.136 AC: 5639 AN: 41498

American (AMR) AF: 0.514 AC: 7845 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1807 AN: 3472

East Asian (EAS) AF: 0.756 AC: 3900 AN: 5162

South Asian (SAS) AF: 0.486 AC: 2345 AN: 4822

European-Finnish (FIN) AF: 0.480 AC: 5057 AN: 10536

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32121 AN: 67960

Other (OTH) AF: 0.429 AC: 907 AN: 2112

Alfa AF: 0.423 Hom.: 2113

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
PhyloP100		-1.6
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: rs12515448; hg19: chr5-162940047;