Genetic Variant ENSG00000251357:p.Ser173Leu (chr22-23894858-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_002415.2(MIF):c.195C>T(p.Ile65Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,554,554 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MIF
NM_002415.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0420

Publications

1 publications found

Variant links:

Genes affected

ENSG00000251357 (HGNC:):

ENSG00000251357 links:

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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12516704).

BP7

Synonymous conserved (PhyloP=-0.042 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002415.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIF	NM_002415.2	MANE Select	c.195C>T	p.Ile65Ile	synonymous	Exon 2 of 3	NP_002406.1	P14174
	MIF-AS1	NR_038911.1		n.1044G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENSG00000251357	ENST00000433835.3	TSL:5	c.518C>T	p.Ser173Leu	missense	Exon 5 of 6	ENSP00000400325.3	H7C1H1
MIF	ENST00000215754.8	TSL:1 MANE Select	c.195C>T	p.Ile65Ile	synonymous	Exon 2 of 3	ENSP00000215754.7	P14174
MIF-AS1	ENST00000406213.1	TSL:1	n.1044G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1402366

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32148

American (AMR)

AF:

0.00

AC:

AN:

37154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25254

East Asian (EAS)

AF:

0.00

AC:

AN:

36534

South Asian (SAS)

AF:

0.00

AC:

AN:

80204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00000184

AC:

AN:

1085674

Other (OTH)

AF:

0.00

AC:

AN:

58350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.84

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.83

PhyloP100

-0.042

PROVEAN

Benign

1.7

REVEL

Benign

0.038

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.033

MutPred

0.28

Loss of glycosylation at S173 (P = 0.0025)

MVP

0.41

ClinPred

0.61

GERP RS

0.25

PromoterAI

0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over