7-1535741-A-G

Variant names:

• chr7-1535741-A-G
• rs3824070
• NM_002360.4:c.-44-3408A>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.-44-3408A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,246 control chromosomes in the GnomAD database, including 32,992 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 (32992 hom., cov: 34)
• Consequence: MAFK NM_002360.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 2 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002360.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAFK	NM_002360.4	MANE Select	c.-44-3408A>G		intron	N/A	NP_002351.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAFK	ENST00000343242.9	TSL:1 MANE Select	c.-44-3408A>G		intron	N/A	ENSP00000344903.4

Frequencies

GnomAD3 genomes AF: 0.651 AC: 99104 AN: 152128 Hom.: 32952 Cov.: 34

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.647

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.652 AC: 99206 AN: 152246 Hom.: 32992 Cov.: 34 AF XY: 0.650 AC XY: 48389 AN XY: 74446

African (AFR) AF: 0.781 AC: 32460 AN: 41554

American (AMR) AF: 0.664 AC: 10157 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1728 AN: 3470

East Asian (EAS) AF: 0.679 AC: 3502 AN: 5158

South Asian (SAS) AF: 0.578 AC: 2793 AN: 4830

European-Finnish (FIN) AF: 0.640 AC: 6795 AN: 10612

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

European-Non Finnish (NFE) AF: 0.582 AC: 39602 AN: 67998

Other (OTH) AF: 0.645 AC: 1363 AN: 2112

Alfa AF: 0.633 Hom.: 4843

Bravo AF: 0.661

Asia WGS AF: 0.643 AC: 2234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.52
DANN	Benign	0.47
PhyloP100		-1.8
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: rs3824070; hg19: chr7-1575377;