chr20-40686030-G-A

Position:

• chr20-40686030-G-A

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.*1849C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 190,674 control chromosomes in the GnomAD database, including 1,204 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: 0.11 (246 hom.)
• Consequence: MAFB NM_005461.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.618

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=-0.46).
• BP6: Variant 20-40686030-G-A is Benign according to our data. Variant chr20-40686030-G-A is described in ClinVar as [Benign]. Clinvar id is 338373.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.*1849C>T		3_prime_UTR_variant	1/1	ENST00000373313.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAFB	ENST00000373313.3	c.*1849C>T		3_prime_UTR_variant	1/1		NM_005461.5	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15592 AN: 151918 Hom.: 958 Cov.: 33

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.176

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.107 AC: 4116 AN: 38638 Hom.: 246 Cov.: 0 AF XY: 0.108 AC XY: 1948 AN XY: 18018

Gnomad4 AFR exome AF: 0.0335

Gnomad4 AMR exome AF: 0.0722

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.0119

Gnomad4 SAS exome AF: 0.0873

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.103 AC: 15585 AN: 152036 Hom.: 958 Cov.: 33 AF XY: 0.104 AC XY: 7736 AN XY: 74296

Gnomad4 AFR AF: 0.0328

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0199

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.107

Alfa AF: 0.121 Hom.: 332

Bravo AF: 0.0950

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	-0.46
CADD	Benign	10
DANN	Benign	0.73

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: rs3577; hg19: chr20-39314670;