20-40685871-A-T

Position:

• chr20-40685871-A-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_005461.5(MAFB):​c.*2008T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 179,978 control chromosomes in the GnomAD database, including 1,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (958 hom., cov: 33)
  • Exomes 𝑓: 0.10 (160 hom.)
• Consequence: MAFB NM_005461.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.24

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 Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 20-40685871-A-T is Benign according to our data. Variant chr20-40685871-A-T is described in ClinVar as [Benign]. Clinvar id is 338372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAFB	NM_005461.5	c.*2008T>A		3_prime_UTR_variant	1/1	ENST00000373313.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAFB	ENST00000373313.3	c.*2008T>A		3_prime_UTR_variant	1/1		NM_005461.5	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15471 AN: 152154 Hom.: 958 Cov.: 33

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.100 AC: 2782 AN: 27706 Hom.: 160 Cov.: 0 AF XY: 0.102 AC XY: 1305 AN XY: 12778

Gnomad4 AFR exome AF: 0.0280

Gnomad4 AMR exome AF: 0.0761

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.0106

Gnomad4 SAS exome AF: 0.0833

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.102 AC: 15464 AN: 152272 Hom.: 958 Cov.: 33 AF XY: 0.103 AC XY: 7684 AN XY: 74458

Gnomad4 AFR AF: 0.0300

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0199

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.107

Alfa AF: 0.114 Hom.: 144

Bravo AF: 0.0939

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56049320; hg19: chr20-39314511;