17-81922946-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_002359.4(MAFG):c.148G>A(p.Val50Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000724 in 1,603,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

MAFG
NM_002359.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.06

Variant links:

Genes affected

MAFG (HGNC:6781): (MAF bZIP transcription factor G) Globin gene expression is regulated through nuclear factor erythroid-2 (NFE2) elements located in enhancer-like locus control regions positioned many kb upstream of alpha- and beta-gene clusters (summarized by Blank et al., 1997 [PubMed 9166829]). NFE2 DNA-binding activity consists of a heterodimer containing a ubiquitous small Maf protein (MafF, MIM 604877; MafG; or MafK, MIM 600197) and the tissue-restricted protein p45 NFE2 (MIM 601490). Both subunits are members of the activator protein-1-like superfamily of basic leucine zipper (bZIP) proteins (see MIM 165160).[supplied by OMIM, Mar 2010]

MAFG links:

ENSG00000264769 (HGNC:56705): (MAFG antisense RNA 1)

ENSG00000264769 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10455555).

BP6

Variant 17-81922946-C-T is Benign according to our data. Variant chr17-81922946-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2516383.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAFG	NM_002359.4 link	c.148G>A	p.Val50Ile	missense_variant	Exon 3 of 3	ENST00000357736.9	NP_002350.1	O15525A0A024R8X1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAFG	ENST00000357736.9 link	c.148G>A	p.Val50Ile	missense_variant	Exon 3 of 3	1	NM_002359.4	ENSP00000350369.4	O15525
MAFG	ENST00000392366.7 link	c.148G>A	p.Val50Ile	missense_variant	Exon 3 of 3	1		ENSP00000376173.3	O15525
MAFG	ENST00000574686.1 link	c.148G>A	p.Val50Ile	missense_variant	Exon 4 of 4	5		ENSP00000459634.1	I3L2F8
ENSG00000264769	ENST00000580897.1 link	n.48C>T		non_coding_transcript_exon_variant	Exon 1 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000395

AC:

AN:

228122

Hom.:

AF XY:

0.0000323

AC XY:

AN XY:

123798

show subpopulations

Gnomad AFR exome

AF:

0.0000708

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000591

Gnomad OTH exome

AF:

0.000354

GnomAD4 exome

AF:

0.0000744

AC:

108

AN:

1450940

Hom.:

Cov.:

AF XY:

0.0000680

AC XY:

AN XY:

720892

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000178

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000822

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 07, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Uncertain

0.42

T;T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.78

.;T;T

M_CAP

Benign

0.068

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.44

N;N;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.11

N;N;.

REVEL

Benign

0.13

Sift

Benign

1.0

T;T;.

Sift4G

Benign

0.98

T;T;.

Polyphen

0.0020

B;B;.

Vest4

0.075

MutPred

0.35

Loss of ubiquitination at K46 (P = 0.0699);Loss of ubiquitination at K46 (P = 0.0699);Loss of ubiquitination at K46 (P = 0.0699);

MVP

0.43

MPC

0.69

ClinPred

0.057

GERP RS

-0.84

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.7

Varity_R

0.010

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over