7-1534767-A-G

Variant names:

• chr7-1534767-A-G
• rs4720833
• NM_002360.4:c.-45+3869A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002360.4(MAFK):​c.-45+3869A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 393,588 control chromosomes in the GnomAD database, including 77,314 homozygotes. 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: 𝑓 0.65 (32685 hom., cov: 32)
  • Exomes 𝑓: 0.60 (44629 hom.)
• Consequence: MAFK NM_002360.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• Publications: 30 publications found

Genes affected

MAFK (HGNC:6782): (MAF bZIP transcription factor K) The developmentally regulated expression of the globin genes depends on upstream regulatory elements termed locus control regions (LCRs). LCRs are associated with powerful enhancer activity that is mediated by the transcription factor NFE2 (nuclear factor erythroid-2). NFE2 recognition sites are also present in the gene promoters of 2 heme biosynthetic enzymes, porphobilinogen deaminase (PBGD; MIM 609806) and ferrochelatase (FECH; MIM 612386). NFE2 DNA-binding activity consists of a heterodimer containing an 18-kD Maf protein (MafF, MafG (MIM 602020), or MafK) and p45 (MIM 601490). Both subunits are members of the activator protein-1 superfamily of basic leucine zipper (bZIP) proteins (see MIM 165160). Maf homodimers suppress transcription at NFE2 sites.[supplied by OMIM, Nov 2008]

LOC100128653 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAFK	NM_002360.4	c.-45+3869A>G		intron_variant	Intron 1 of 2	ENST00000343242.9	NP_002351.1
LOC100128653	NR_149036.1	n.114T>C		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAFK	ENST00000343242.9	c.-45+3869A>G		intron_variant	Intron 1 of 2	1	NM_002360.4	ENSP00000344903.4

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98626 AN: 151866 Hom.: 32645 Cov.: 32

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.647

GnomAD2 exomes AF: 0.631 AC: 56692 AN: 89912 AF XY: 0.623

Gnomad AFR exome AF: 0.769

Gnomad AMR exome AF: 0.706

Gnomad ASJ exome AF: 0.517

Gnomad EAS exome AF: 0.665

Gnomad FIN exome AF: 0.673

Gnomad NFE exome AF: 0.588

Gnomad OTH exome AF: 0.615

GnomAD4 exome AF: 0.604 AC: 145938 AN: 241604 Hom.: 44629 Cov.: 0 AF XY: 0.599 AC XY: 80336 AN XY: 134082

African (AFR) AF: 0.767 AC: 5358 AN: 6988

American (AMR) AF: 0.706 AC: 14276 AN: 20218

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 3505 AN: 6920

East Asian (EAS) AF: 0.666 AC: 5615 AN: 8436

South Asian (SAS) AF: 0.577 AC: 29794 AN: 51614

European-Finnish (FIN) AF: 0.660 AC: 6852 AN: 10376

Middle Eastern (MID) AF: 0.580 AC: 1416 AN: 2440

European-Non Finnish (NFE) AF: 0.587 AC: 72289 AN: 123194

Other (OTH) AF: 0.598 AC: 6833 AN: 11418

GnomAD4 genome AF: 0.650 AC: 98724 AN: 151984 Hom.: 32685 Cov.: 32 AF XY: 0.648 AC XY: 48136 AN XY: 74268

African (AFR) AF: 0.773 AC: 32062 AN: 41464

American (AMR) AF: 0.663 AC: 10122 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1742 AN: 3464

East Asian (EAS) AF: 0.679 AC: 3486 AN: 5136

South Asian (SAS) AF: 0.578 AC: 2783 AN: 4814

European-Finnish (FIN) AF: 0.640 AC: 6770 AN: 10570

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39589 AN: 67950

Other (OTH) AF: 0.645 AC: 1364 AN: 2114

Alfa AF: 0.604 Hom.: 107414

Bravo AF: 0.659

Asia WGS AF: 0.643 AC: 2235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.94
DANN	Benign	0.33
PhyloP100		-0.035
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: rs4720833; hg19: chr7-1574403; COSMIC: COSV58345161; COSMIC: COSV58345161;