20-40686359-G-C

Position:

• chr20-40686359-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005461.5(MAFB):​c.*1520C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00805 in 262,282 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (36 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (5 hom.)
• Consequence: MAFB NM_005461.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0110

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 20-40686359-G-C is Benign according to our data. Variant chr20-40686359-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 338383.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1843/152060) while in subpopulation AFR AF= 0.0409 (1696/41486). AF 95% confidence interval is 0.0393. There are 36 homozygotes in gnomad4. There are 874 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1843 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAFB	NM_005461.5	c.*1520C>G		3_prime_UTR_variant	1/1	ENST00000373313.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAFB	ENST00000373313.3	c.*1520C>G		3_prime_UTR_variant	1/1		NM_005461.5	P1

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1836 AN: 151942 Hom.: 36 Cov.: 33

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00544

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.000418

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.00244 AC: 269 AN: 110222 Hom.: 5 Cov.: 0 AF XY: 0.00210 AC XY: 111 AN XY: 52750

Gnomad4 AFR exome AF: 0.0375

Gnomad4 AMR exome AF: 0.00490

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000492

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000365

Gnomad4 NFE exome AF: 0.000451

Gnomad4 OTH exome AF: 0.00350

GnomAD4 genome AF: 0.0121 AC: 1843 AN: 152060 Hom.: 36 Cov.: 33 AF XY: 0.0118 AC XY: 874 AN XY: 74352

Gnomad4 AFR AF: 0.0409

Gnomad4 AMR AF: 0.00543

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.000419

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.0000707 Hom.: 0

Bravo AF: 0.0143

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Likely 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	-0.86
CADD	Benign	0.59
DANN	Benign	0.60

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: rs148352161; hg19: chr20-39314999;