Genetic Variant MAFB:c.*1592dupT (chr20-40686286-G-GA) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_005461.5(MAFB):c.*1592dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.007 in 204,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 22)

Exomes 𝑓: 0.025 ( 0 hom. )

Consequence

MAFB
NM_005461.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

MAFB (HGNC:6408): (MAF bZIP transcription factor B) The protein encoded by this gene is a basic leucine zipper (bZIP) transcription factor that plays an important role in the regulation of lineage-specific hematopoiesis. The encoded nuclear protein represses ETS1-mediated transcription of erythroid-specific genes in myeloid cells. This gene contains no introns. [provided by RefSeq, Jul 2008]

MAFB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0249 (1395/56074) while in subpopulation MID AF = 0.0316 (10/316). AF 95% confidence interval is 0.0272. There are 0 homozygotes in GnomAdExome4. There are 677 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position FAILED quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAFB	NM_005461.5 link	c.*1592dupT		3_prime_UTR_variant	Exon 1 of 1	ENST00000373313.3	NP_005452.2	Q9Y5Q3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAFB	ENST00000373313 link	c.*1592dupT		3_prime_UTR_variant	Exon 1 of 1		NM_005461.5	ENSP00000362410.2		Q9Y5Q3

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

147854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000172

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000270

Gnomad ASJ

AF:

0.00263

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000180

Gnomad OTH

AF:

0.000496

GnomAD4 exome

AF:

0.0249

AC:

1395

AN:

56074

Hom.:

Cov.:

AF XY:

0.0257

AC XY:

677

AN XY:

26314

show subpopulations

Gnomad4 AFR exome

AF:

0.00861

AC:

AN:

2672

Gnomad4 AMR exome

AF:

0.0270

AC:

AN:

1702

Gnomad4 ASJ exome

AF:

0.0297

AC:

100

AN:

3368

Gnomad4 EAS exome

AF:

0.0114

AC:

AN:

7974

Gnomad4 SAS exome

AF:

0.0126

AC:

AN:

476

Gnomad4 FIN exome

AF:

0.0105

AC:

AN:

570

Gnomad4 NFE exome

AF:

0.0287

AC:

987

AN:

34348

Gnomad4 Remaining exome

AF:

0.0271

AC:

126

AN:

4648

⚠️ The allele balance in gnomAD4 Exomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Heterozygous variant carriers

176

353

529

706

882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000230

AC:

AN:

147958

Hom.:

Cov.:

AF XY:

0.000195

AC XY:

AN XY:

71962

show subpopulations

Gnomad4 AFR

AF:

0.000171

AC:

0.000171116

AN:

0.000171116

Gnomad4 AMR

AF:

0.000270

AC:

0.000269724

AN:

0.000269724

Gnomad4 ASJ

AF:

0.00263

AC:

0.0026285

AN:

0.0026285

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000213

AC:

0.000213402

AN:

0.000213402

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000181

AC:

0.000180516

AN:

0.000180516

Gnomad4 OTH

AF:

0.000491

AC:

0.000490677

AN:

0.000490677

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000747

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Multicentric carpo-tarsal osteolysis with or without nephropathy

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over