chr22-23894794-C-G

Variant names:

• chr22-23894794-C-G
• rs11548059
• NM_002415.2:c.131C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002415.2(MIF):​c.131C>G​(p.Pro44Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,398,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: MIF NM_002415.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.49

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.895

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIF	NM_002415.2	c.131C>G	p.Pro44Arg	missense_variant	Exon 2 of 3	ENST00000215754.8	NP_002406.1
MIF-AS1	NR_038911.1	n.1108G>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIF	ENST00000215754.8	c.131C>G	p.Pro44Arg	missense_variant	Exon 2 of 3	1	NM_002415.2	ENSP00000215754.7
ENSG00000251357	ENST00000433835.3	c.454C>G	p.Arg152Gly	missense_variant	Exon 5 of 6	5		ENSP00000400325.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1398686 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 690512

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000553

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	D
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.44	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.027	D
Polyphen		1.0	D
Vest4		0.80
MutPred		0.67		Gain of sheet (P = 0.0827);
MVP		0.72
MPC		1.8
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.95
gMVP		0.69

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: rs11548059; hg19: chr22-24236981;