Variant 22-23894887-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_002415.2(MIF):c.224C>T(p.Ser75Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,553,982 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 5 hom. )

Consequence

MIF
NM_002415.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.658

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:

ENSG00000251357 (HGNC:):

ENSG00000251357 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01174289).

BP6

Variant 22-23894887-C-T is Benign according to our data. Variant chr22-23894887-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3049829.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIF	NM_002415.2 linkuse as main transcript	c.224C>T	p.Ser75Phe	missense_variant	2/3	ENST00000215754.8	NP_002406.1	P14174I4AY87
MIF-AS1	NR_038911.1 linkuse as main transcript	n.1015G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIF	ENST00000215754.8 linkuse as main transcript	c.224C>T	p.Ser75Phe	missense_variant	2/3	1	NM_002415.2	ENSP00000215754.7		P14174
ENSG00000251357	ENST00000433835.3 linkuse as main transcript	c.547C>T	p.Pro183Ser	missense_variant	5/6	5		ENSP00000400325.3		H7C1H1

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

195

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00203

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00138

AC:

206

AN:

149230

Hom.:

AF XY:

0.00145

AC XY:

119

AN XY:

81840

show subpopulations

Gnomad AFR exome

AF:

0.000423

Gnomad AMR exome

AF:

0.000477

Gnomad ASJ exome

AF:

0.000242

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00242

Gnomad FIN exome

AF:

0.00190

Gnomad NFE exome

AF:

0.00183

Gnomad OTH exome

AF:

0.000945

GnomAD4 exome

AF:

0.00155

AC:

2176

AN:

1401708

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1101

AN XY:

692482

show subpopulations

Gnomad4 AFR exome

AF:

0.000344

Gnomad4 AMR exome

AF:

0.000629

Gnomad4 ASJ exome

AF:

0.000476

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00198

Gnomad4 FIN exome

AF:

0.00186

Gnomad4 NFE exome

AF:

0.00166

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.00127

AC:

194

AN:

152274

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00203

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.00113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000895

AC:

ExAC

AF:

0.000844

AC:

Asia WGS

AF:

0.000868

AC:

AN:

3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MIF-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 03, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.42

M_CAP

Benign

0.013

MetaRNN

Benign

0.012

Sift4G

Benign

0.34

MVP

0.095

ClinPred

0.037

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

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