rs4824562

Variant names:

• chrX-43844544-T-C
• rs4824562
• NM_000898.5:c.47-780A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000898.5(MAOB):​c.47-780A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 111,444 control chromosomes in the GnomAD database, including 739 homozygotes. There are 4,148 hemizygotes in GnomAD. 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 0.12 (739 hom., 4141 hem., cov: 23)
  • Exomes 𝑓: 0.34 (0 hom. 7 hem.)
• Consequence: MAOB NM_000898.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 5 publications found

Genes affected

MAOB (HGNC:6834): (monoamine oxidase B) The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is a enzyme located in the mitochondrial outer membrane. It catalyzes the oxidative deamination of biogenic and xenobiotic amines and plays an important role in the metabolism of neuroactive and vasoactive amines in the central nervous sysytem and peripheral tissues. This protein preferentially degrades benzylamine and phenylethylamine. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOB	NM_000898.5	c.47-780A>G		intron_variant	Intron 1 of 14	ENST00000378069.5	NP_000889.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOB	ENST00000378069.5	c.47-780A>G		intron_variant	Intron 1 of 14	1	NM_000898.5	ENSP00000367309.4
MAOB	ENST00000468431.1	n.152A>G		non_coding_transcript_exon_variant	Exon 2 of 3	3
MAOB	ENST00000487544.1	n.284A>G		non_coding_transcript_exon_variant	Exon 2 of 7	5

Frequencies

GnomAD3 genomes AF: 0.124 AC: 13839 AN: 111364 Hom.: 738 Cov.: 23

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.0502

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.345 AC: 10 AN: 29 Hom.: 0 Cov.: 0 AF XY: 0.467 AC XY: 7 AN XY: 15

African (AFR) AC: 0 AN: 0

American (AMR) AF: 1.00 AC: 1 AN: 1

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.321 AC: 9 AN: 28

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.124 AC: 13839 AN: 111415 Hom.: 739 Cov.: 23 AF XY: 0.123 AC XY: 4141 AN XY: 33627

African (AFR) AF: 0.0315 AC: 968 AN: 30770

American (AMR) AF: 0.175 AC: 1847 AN: 10555

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 278 AN: 2640

East Asian (EAS) AF: 0.145 AC: 509 AN: 3516

South Asian (SAS) AF: 0.218 AC: 574 AN: 2633

European-Finnish (FIN) AF: 0.181 AC: 1079 AN: 5948

Middle Eastern (MID) AF: 0.0459 AC: 10 AN: 218

European-Non Finnish (NFE) AF: 0.154 AC: 8177 AN: 52963

Other (OTH) AF: 0.121 AC: 182 AN: 1506

Alfa AF: 0.138 Hom.: 6955

Bravo AF: 0.120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.8
DANN	Benign	0.89
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs4824562; hg19: chrX-43703790; COSMIC: COSV65207213;