Genetic Variant ENSG00000251357:c.432-600C>G (chr22-23894172-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000433835.3(ENSG00000251357):c.432-600C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 539,296 control chromosomes in the GnomAD database, including 229 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 0.027 ( 167 hom., cov: 33)

Exomes 𝑓: 0.0062 ( 62 hom. )

Consequence

ENSG00000251357
ENST00000433835.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.00

Publications

8 publications found

Variant links:

Genes affected

ENSG00000251357 (HGNC:):

ENSG00000251357 links:

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

MIF-AS1 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 Gene-Disease associations (from GenCC):

cystic fibrosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MIF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIF-AS1	NR_038911.1 link	n.1730G>C		non_coding_transcript_exon_variant	Exon 3 of 3
MIF	NM_002415.2 link	c.-303C>G		upstream_gene_variant		ENST00000215754.8	NP_002406.1	P14174I4AY87

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENSG00000251357	ENST00000433835.3 link	c.432-600C>G	intron_variant	Intron 4 of 5	5		ENSP00000400325.3	H7C1H1
ENSG00000290199	ENST00000717616.1 link	n.213-2706G>C	intron_variant	Intron 2 of 2
MIF	ENST00000215754.8 link	c.-303C>G	upstream_gene_variant		1	NM_002415.2	ENSP00000215754.7	P14174

Frequencies

GnomAD3 genomes

AF:

0.0272

AC:

4139

AN:

152290

Hom.:

162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0898

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0302

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000411

Gnomad OTH

AF:

0.0205

GnomAD4 exome

AF:

0.00618

AC:

2392

AN:

386888

Hom.:

Cov.:

AF XY:

0.00747

AC XY:

1531

AN XY:

205058

show subpopulations

African (AFR)

AF:

0.0848

AC:

625

AN:

7374

American (AMR)

AF:

0.0107

AC:

140

AN:

13104

Ashkenazi Jewish (ASJ)

AF:

0.00131

AC:

AN:

11444

East Asian (EAS)

AF:

0.00

AC:

AN:

24258

South Asian (SAS)

AF:

0.0305

AC:

1277

AN:

41904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27122

Middle Eastern (MID)

AF:

0.00413

AC:

AN:

1696

European-Non Finnish (NFE)

AF:

0.000358

AC:

AN:

237416

Other (OTH)

AF:

0.0108

AC:

243

AN:

22570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

111

222

332

443

554

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:

0.0273

AC:

4161

AN:

152408

Hom.:

167

Cov.:

AF XY:

0.0268

AC XY:

1999

AN XY:

74532

show subpopulations

African (AFR)

AF:

0.0900

AC:

3746

AN:

41600

American (AMR)

AF:

0.0125

AC:

192

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.0302

AC:

146

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000411

AC:

AN:

68046

Other (OTH)

AF:

0.0203

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

215

430

645

860

1075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0162

Hom.:

Bravo

AF:

0.0310

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.78

(source)

DANN

Benign

0.52

PhyloP100

-2.0

PromoterAI

0.42

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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