Variant 22-23894884-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000215754.8(MIF):c.221G>T(p.Arg74Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000714 in 1,400,726 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R74G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

MIF
ENST00000215754.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.03

Variant links:

Genes affected

MIF (HGNC:7097): (macrophage migration inhibitory factor) This gene encodes a lymphokine involved in cell-mediated immunity, immunoregulation, and inflammation. It plays a role in the regulation of macrophage function in host defense through the suppression of anti-inflammatory effects of glucocorticoids. This lymphokine and the JAB1 protein form a complex in the cytosol near the peripheral plasma membrane, which may indicate an additional role in integrin signaling pathways. [provided by RefSeq, Jul 2008]

MIF links:

MIF-AS1 (HGNC:27669): (MIF antisense RNA 1)

MIF-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIF	NM_002415.2 linkuse as main transcript	c.221G>T	p.Arg74Leu	missense_variant	2/3	ENST00000215754.8	NP_002406.1
MIF-AS1	NR_038911.1 linkuse as main transcript	n.1018C>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MIF	ENST00000215754.8 linkuse as main transcript	c.221G>T	p.Arg74Leu	missense_variant	2/3	1	NM_002415.2	ENSP00000215754	P1
MIF-AS1	ENST00000406213.1 linkuse as main transcript	n.1018C>A		non_coding_transcript_exon_variant	3/3	1
MIF	ENST00000465752.1 linkuse as main transcript	n.246G>T		non_coding_transcript_exon_variant	2/2	1
MIF	ENST00000498385.1 linkuse as main transcript	n.187G>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.14e-7

AC:

AN:

1400726

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

691994

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.221G>T (p.R74L) alteration is located in exon 2 (coding exon 2) of the MIF gene. This alteration results from a G to T substitution at nucleotide position 221, causing the arginine (R) at amino acid position 74 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Benign

-0.015

Eigen_PC

Benign

0.067

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.066

MetaRNN

Uncertain

0.74

MutationTaster

Benign

1.0

Sift4G

Benign

0.46

MVP

0.11

ClinPred

0.97

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over