chr22-23894632-T-C

Variant names:

• chr22-23894632-T-C
• rs2096525
• ENST00000406213.1:n.1270A>G

Variant summary

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

The ENST00000406213.1(MIF-AS1):​n.1270A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,488,392 control chromosomes in the GnomAD database, including 26,303 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 0.20 (3133 hom., cov: 31)
  • Exomes 𝑓: 0.19 (23170 hom.)
• Consequence: MIF-AS1 ENST00000406213.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 30 publications found

Genes affected

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

ENSG00000251357 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000406213.1. 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	NM_002415.2	MANE Select	c.108+50T>C		intron	N/A	NP_002406.1
	MIF-AS1	NR_038911.1		n.1270A>G		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIF-AS1	ENST00000406213.1	TSL:1	n.1270A>G		non_coding_transcript_exon	Exon 3 of 3
	MIF	ENST00000215754.8	TSL:1 MANE Select	c.108+50T>C		intron	N/A	ENSP00000215754.7
	ENSG00000251357	ENST00000433835.3	TSL:5	c.432-140T>C		intron	N/A	ENSP00000400325.3

Frequencies

GnomAD3 genomes AF: 0.204 AC: 29894 AN: 146614 Hom.: 3125 Cov.: 31

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.184

GnomAD2 exomes AF: 0.203 AC: 43115 AN: 212084 AF XY: 0.201

Gnomad AFR exome AF: 0.221

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.196

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.187 AC: 251191 AN: 1341642 Hom.: 23170 Cov.: 25 AF XY: 0.188 AC XY: 125602 AN XY: 669646

African (AFR) AF: 0.230 AC: 7139 AN: 31082

American (AMR) AF: 0.278 AC: 11399 AN: 41060

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 3540 AN: 23334

East Asian (EAS) AF: 0.205 AC: 7130 AN: 34712

South Asian (SAS) AF: 0.229 AC: 19064 AN: 83366

European-Finnish (FIN) AF: 0.243 AC: 10885 AN: 44862

Middle Eastern (MID) AF: 0.170 AC: 763 AN: 4484

European-Non Finnish (NFE) AF: 0.176 AC: 180693 AN: 1023990

Other (OTH) AF: 0.193 AC: 10578 AN: 54752

GnomAD4 genome AF: 0.204 AC: 29928 AN: 146750 Hom.: 3133 Cov.: 31 AF XY: 0.209 AC XY: 14958 AN XY: 71494

African (AFR) AF: 0.229 AC: 9283 AN: 40528

American (AMR) AF: 0.241 AC: 3587 AN: 14890

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 458 AN: 3416

East Asian (EAS) AF: 0.207 AC: 943 AN: 4550

South Asian (SAS) AF: 0.250 AC: 1084 AN: 4344

European-Finnish (FIN) AF: 0.248 AC: 2389 AN: 9628

Middle Eastern (MID) AF: 0.178 AC: 51 AN: 286

European-Non Finnish (NFE) AF: 0.175 AC: 11589 AN: 66152

Other (OTH) AF: 0.181 AC: 374 AN: 2066

Alfa AF: 0.182 Hom.: 533

Bravo AF: 0.196

Asia WGS AF: 0.224 AC: 779 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		-1.9
PromoterAI		-0.092	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2096525; hg19: chr22-24236819; COSMIC: COSV53158871; COSMIC: COSV53158871;