dbSNP rs17004038: MIF:c.-71C>A (chr22-23894404-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_002415.2(MIF):c.-71C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000789 in 1,277,038 control chromosomes in the GnomAD database, including 11 homozygotes. 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 0.00083 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00078 ( 8 hom. )

Consequence

MIF
NM_002415.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.52

Publications

7 publications found

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:

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

MIF-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000827 (126/152338) while in subpopulation EAS AF = 0.0218 (113/5182). AF 95% confidence interval is 0.0185. There are 3 homozygotes in GnomAd4. There are 60 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIF	NM_002415.2 link	c.-71C>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000215754.8	NP_002406.1	P14174I4AY87
MIF-AS1	NR_038911.1 link	n.1498G>T		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 link	c.-71C>A		5_prime_UTR_variant	Exon 1 of 3	1	NM_002415.2	ENSP00000215754.7		P14174
ENSG00000251357	ENST00000433835.3 link	c.432-368C>A		intron_variant	Intron 4 of 5	5		ENSP00000400325.3		H7C1H1

Frequencies

GnomAD3 genomes

AF:

0.000834

AC:

127

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0219

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000784

AC:

882

AN:

1124700

Hom.:

Cov.:

AF XY:

0.000742

AC XY:

426

AN XY:

573954

show subpopulations

African (AFR)

AF:

0.0000372

AC:

AN:

26862

American (AMR)

AF:

0.00

AC:

AN:

42144

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23722

East Asian (EAS)

AF:

0.0213

AC:

801

AN:

37682

South Asian (SAS)

AF:

0.000178

AC:

AN:

78434

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5130

European-Non Finnish (NFE)

AF:

0.00000617

AC:

AN:

810618

Other (OTH)

AF:

0.00124

AC:

AN:

49044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

107

161

214

268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000827

AC:

126

AN:

152338

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41578

American (AMR)

AF:

0.000131

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0218

AC:

113

AN:

5182

South Asian (SAS)

AF:

0.000828

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000245

Hom.:

Bravo

AF:

0.000835

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

1.5

PromoterAI

-0.027

Neutral

(source)

Mutation Taster

=298/2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over