7-1535741-A-G

Position:

• chr7-1535741-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAFK	NM_002360.4	c.-44-3408A>G		intron_variant		ENST00000343242.9	NP_002351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAFK	ENST00000343242.9	c.-44-3408A>G		intron_variant		1	NM_002360.4	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

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.645

Alfa AF: 0.629 Hom.: 4625

Bravo AF: 0.661

Asia WGS AF: 0.643 AC: 2234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.52
DANN	Benign	0.47

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: rs3824070; hg19: chr7-1575377;