22-23894205-G-C

Variant names:

• chr22-23894205-G-C
• rs755622
• ENST00000433835.3:c.432-567G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000433835.3(ENSG00000251357):​c.432-567G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 575,612 control chromosomes in the GnomAD database, including 14,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.25 (5807 hom., cov: 34)
  • Exomes 𝑓: 0.19 (8518 hom.)
• Consequence: ENSG00000251357 ENST00000433835.3 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.948
• Publications: 377 publications found

Genes affected

ENSG00000251357 (HGNC:):

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

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000433835.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIF-AS1	NR_038911.1		n.1697C>G		non_coding_transcript_exon	Exon 3 of 3
	MIF	NM_002415.2	MANE Select	c.-270G>C		upstream_gene	N/A	NP_002406.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000251357	ENST00000433835.3	TSL:5	c.432-567G>C		intron	N/A	ENSP00000400325.3
	ENSG00000290199	ENST00000717616.1		n.213-2739C>G		intron	N/A
	MIF	ENST00000215754.8	TSL:1 MANE Select	c.-270G>C		upstream_gene	N/A	ENSP00000215754.7

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38654 AN: 152146 Hom.: 5790 Cov.: 34

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.192 AC: 81356 AN: 423348 Hom.: 8518 Cov.: 0 AF XY: 0.194 AC XY: 43705 AN XY: 225798

African (AFR) AF: 0.402 AC: 3446 AN: 8574

American (AMR) AF: 0.261 AC: 4138 AN: 15866

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 1819 AN: 12302

East Asian (EAS) AF: 0.212 AC: 5731 AN: 27060

South Asian (SAS) AF: 0.230 AC: 10212 AN: 44452

European-Finnish (FIN) AF: 0.230 AC: 6616 AN: 28776

Middle Eastern (MID) AF: 0.189 AC: 350 AN: 1850

European-Non Finnish (NFE) AF: 0.169 AC: 44025 AN: 259948

Other (OTH) AF: 0.205 AC: 5019 AN: 24520

GnomAD4 genome AF: 0.254 AC: 38720 AN: 152264 Hom.: 5807 Cov.: 34 AF XY: 0.257 AC XY: 19136 AN XY: 74440

African (AFR) AF: 0.410 AC: 17047 AN: 41550

American (AMR) AF: 0.262 AC: 4011 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 525 AN: 3466

East Asian (EAS) AF: 0.201 AC: 1040 AN: 5182

South Asian (SAS) AF: 0.233 AC: 1123 AN: 4828

European-Finnish (FIN) AF: 0.232 AC: 2463 AN: 10610

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11808 AN: 68010

Other (OTH) AF: 0.219 AC: 464 AN: 2116

Alfa AF: 0.227 Hom.: 587

Bravo AF: 0.259

Asia WGS AF: 0.252 AC: 877 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

RHEUMATOID ARTHRITIS, SYSTEMIC JUVENILE, SUSCEPTIBILITY TO Other:1

May 01, 2003

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.45
PhyloP100		-0.95
PromoterAI		0.084	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs755622; hg19: chr22-24236392;