NM_005461.5:c.*1849C>T

Variant names:

• chr20-40686030-G-A
• rs3577
• NM_005461.5:c.*1849C>T

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.*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
• Publications: 8 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: Benign. The variant received -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 VariationId 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.

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.*1849C>T		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.*1849C>T		3_prime_UTR	Exon 1 of 1	ENSP00000362410.2	Q9Y5Q3

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

African (AFR) AF: 0.0335 AC: 50 AN: 1494

American (AMR) AF: 0.0722 AC: 69 AN: 956

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 258 AN: 2422

East Asian (EAS) AF: 0.0119 AC: 80 AN: 6750

South Asian (SAS) AF: 0.0873 AC: 29 AN: 332

European-Finnish (FIN) AF: 0.144 AC: 66 AN: 458

Middle Eastern (MID) AF: 0.175 AC: 40 AN: 228

European-Non Finnish (NFE) AF: 0.139 AC: 3169 AN: 22842

Other (OTH) AF: 0.112 AC: 355 AN: 3156

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

African (AFR) AF: 0.0328 AC: 1360 AN: 41484

American (AMR) AF: 0.107 AC: 1634 AN: 15276

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

East Asian (EAS) AF: 0.0199 AC: 103 AN: 5184

South Asian (SAS) AF: 0.106 AC: 512 AN: 4808

European-Finnish (FIN) AF: 0.145 AC: 1525 AN: 10542

Middle Eastern (MID) AF: 0.176 AC: 51 AN: 290

European-Non Finnish (NFE) AF: 0.142 AC: 9670 AN: 67962

Other (OTH) AF: 0.107 AC: 226 AN: 2108

Alfa AF: 0.119 Hom.: 334

Bravo AF: 0.0950

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.46
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

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: rs3577; hg19: chr20-39314670;