chr22-23894884-G-T

Position:

• chr22-23894884-G-T

Variant summary

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

The NM_002415.2(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 (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: MIF NM_002415.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.03

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]

ENSG00000251357 (HGNC:):

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

ACMG classification

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	c.221G>T	p.Arg74Leu	missense_variant	2/3	ENST00000215754.8	NP_002406.1
MIF-AS1	NR_038911.1	n.1018C>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIF	ENST00000215754.8	c.221G>T	p.Arg74Leu	missense_variant	2/3	1	NM_002415.2	ENSP00000215754.7
ENSG00000251357	ENST00000433835.3	c.544G>T	p.Ala182Ser	missense_variant	5/6	5		ENSP00000400325.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400726 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 691994

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.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Benign	-0.015
Eigen_PC	Benign	0.067
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.74	D
Sift4G	Benign	0.46	T
MVP		0.11
ClinPred		0.97	D
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.

Other links and lift over

hg19: chr22-24237071;