20-40686128-G-T

Variant names:

• chr20-40686128-G-T
• rs886056656
• NM_005461.5:c.*1751C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005461.5(MAFB):​c.*1751C>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0000203 in 49,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: MAFB NM_005461.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.52
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 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, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).

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.*1751C>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.*1751C>A		3_prime_UTR	Exon 1 of 1	ENSP00000362410.2	Q9Y5Q3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000203 AC: 1 AN: 49348 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 22910

African (AFR) AF: 0.00 AC: 0 AN: 2062

American (AMR) AF: 0.00 AC: 0 AN: 1314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3200

East Asian (EAS) AF: 0.00 AC: 0 AN: 7764

South Asian (SAS) AF: 0.00 AC: 0 AN: 408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.0000336 AC: 1 AN: 29786

Other (OTH) AF: 0.00 AC: 0 AN: 4046

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.87
PhyloP100		4.5

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

Other links and lift over

dbSNP: rs886056656; hg19: chr20-39314768;