rs7733775

Positions:

• chr5-163517703-A-G
• chr5-163517703-A-T

Variant summary

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

The ENST00000518095.5(MAT2B):​c.*932A>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 0.583 in 1,335,750 control chromosomes in the GnomAD database, including 232,507 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 0.50 (21473 hom., cov: 32)
  • Exomes 𝑓: 0.59 (211034 hom.)
• Consequence: MAT2B ENST00000518095.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAT2B	NM_013283.5	c.834+29A>G		intron_variant		ENST00000321757.11
MAT2B	NM_182796.2	c.801+29A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAT2B	ENST00000321757.11	c.834+29A>G		intron_variant		1	NM_013283.5	P1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76361 AN: 151930 Hom.: 21468 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.533

GnomAD3 exomes AF: 0.602 AC: 148951 AN: 247536 Hom.: 46473 AF XY: 0.605 AC XY: 80999 AN XY: 133776

Gnomad AFR exome AF: 0.242

Gnomad AMR exome AF: 0.674

Gnomad ASJ exome AF: 0.618

Gnomad EAS exome AF: 0.815

Gnomad SAS exome AF: 0.650

Gnomad FIN exome AF: 0.617

Gnomad NFE exome AF: 0.578

Gnomad OTH exome AF: 0.595

GnomAD4 exome AF: 0.593 AC: 702299 AN: 1183702 Hom.: 211034 Cov.: 16 AF XY: 0.596 AC XY: 359420 AN XY: 602768

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.669

Gnomad4 ASJ exome AF: 0.618

Gnomad4 EAS exome AF: 0.796

Gnomad4 SAS exome AF: 0.648

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.586

Gnomad4 OTH exome AF: 0.581

GnomAD4 genome AF: 0.502 AC: 76374 AN: 152048 Hom.: 21473 Cov.: 32 AF XY: 0.509 AC XY: 37862 AN XY: 74330

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.534

Alfa AF: 0.534 Hom.: 7729

Bravo AF: 0.487

Asia WGS AF: 0.624 AC: 2170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.77

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: rs7733775; hg19: chr5-162944709; COSMIC: COSV55200220; COSMIC: COSV55200220;