20-40686286-G-GA

Position:

• chr20-40686286-G-GA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_005461.5(MAFB):​c.*1592_*1593insT 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome 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 gnomad4_exome. There are 677 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck. 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/exons	MANE	UniProt
MAFB	NM_005461.5	c.*1592_*1593insT		3_prime_UTR_variant	1/1	ENST00000373313.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAFB	ENST00000373313.3	c.*1592_*1593insT		3_prime_UTR_variant	1/1		NM_005461.5	P1

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 34 AN: 147854 Hom.: 0 Cov.: 22

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.: 0 Cov.: 0 AF XY: 0.0257 AC XY: 677 AN XY: 26314

Gnomad4 AFR exome AF: 0.00861

Gnomad4 AMR exome AF: 0.0270

Gnomad4 ASJ exome AF: 0.0297

Gnomad4 EAS exome AF: 0.0114

Gnomad4 SAS exome AF: 0.0126

Gnomad4 FIN exome AF: 0.0105

Gnomad4 NFE exome AF: 0.0287

Gnomad4 OTH exome AF: 0.0271

GnomAD4 genome AF: 0.000230 AC: 34 AN: 147958 Hom.: 0 Cov.: 22 AF XY: 0.000195 AC XY: 14 AN XY: 71962

Gnomad4 AFR AF: 0.000171

Gnomad4 AMR AF: 0.000270

Gnomad4 ASJ AF: 0.00263

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000181

Gnomad4 OTH AF: 0.000491

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Multicentric carpo-tarsal osteolysis with or without nephropathy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs3215567; hg19: chr20-39314926;