rs57122772

Positions:

• chr5-163505473-T-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874

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=-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/exons	MANE	Protein	UniProt
MAT2B	NM_182796.2	c.30+2049T>G		intron_variant			NP_877725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAT2B	ENST00000280969.9	c.30+2049T>G		intron_variant		1		ENSP00000280969
MAT2B	ENST00000694938.1	c.30+2049T>G		intron_variant				ENSP00000511605
MAT2B	ENST00000694939.1	c.30+2049T>G		intron_variant				ENSP00000511606

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 5104 AN: 152208 Hom.: 251 Cov.: 32

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

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000551

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000145

Gnomad4 OTH exome AF: 0.00780

GnomAD4 genome AF: 0.0336 AC: 5117 AN: 152326 Hom.: 252 Cov.: 32 AF XY: 0.0340 AC XY: 2534 AN XY: 74500

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0263 Hom.: 20

Bravo AF: 0.0380

Asia WGS AF: 0.00549 AC: 19 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
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs57122772; hg19: chr5-162932479;