rs56049320

Variant names:

• chr20-40685871-A-T
• rs56049320
• NM_005461.5:c.*2008T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• multicentric carpo-tarsal osteolysis with or without nephropathy

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• Duane retraction syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet
• Duane retraction syndrome 3 with or without deafness

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005461.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAFB	NM_005461.5	MANE Select	c.*2008T>A		3_prime_UTR	Exon 1 of 1	NP_005452.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAFB	ENST00000373313.3	TSL:6 MANE Select	c.*2008T>A		3_prime_UTR	Exon 1 of 1	ENSP00000362410.2	Q9Y5Q3

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

African (AFR) AF: 0.0280 AC: 25 AN: 892

American (AMR) AF: 0.0761 AC: 47 AN: 618

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 179 AN: 1750

East Asian (EAS) AF: 0.0106 AC: 61 AN: 5732

South Asian (SAS) AF: 0.0833 AC: 19 AN: 228

European-Finnish (FIN) AF: 0.138 AC: 51 AN: 370

Middle Eastern (MID) AF: 0.169 AC: 27 AN: 160

European-Non Finnish (NFE) AF: 0.136 AC: 2135 AN: 15736

Other (OTH) AF: 0.107 AC: 238 AN: 2220

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

African (AFR) AF: 0.0300 AC: 1247 AN: 41580

American (AMR) AF: 0.106 AC: 1620 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3472

East Asian (EAS) AF: 0.0199 AC: 103 AN: 5182

South Asian (SAS) AF: 0.107 AC: 515 AN: 4808

European-Finnish (FIN) AF: 0.143 AC: 1520 AN: 10600

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9674 AN: 68004

Other (OTH) AF: 0.107 AC: 227 AN: 2116

Alfa AF: 0.114 Hom.: 144

Bravo AF: 0.0939

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Multicentric carpo-tarsal osteolysis with or without nephropathy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56049320; hg19: chr20-39314511;