rs2096525

chr22-23894632-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002415.2(MIF):c.108+50T>C variant causes a intron 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 NM_002415.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIF	NM_002415.2	c.108+50T>C		intron_variant		ENST00000215754.8
MIF-AS1	NR_038911.1	n.1270A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIF	ENST00000215754.8	c.108+50T>C		intron_variant		1	NM_002415.2	P1
MIF-AS1	ENST00000406213.1	n.1270A>G		non_coding_transcript_exon_variant	3/3	1
MIF	ENST00000465752.1	n.133+50T>C		intron_variant, non_coding_transcript_variant		1

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

GnomAD3 exomes AF: 0.203 AC: 43115 AN: 212084 Hom.: 4604 AF XY: 0.201 AC XY: 23531 AN XY: 117326

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 SAS exome AF: 0.226

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

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.193

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

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.181

Alfa AF: 0.181 Hom.: 519

Bravo AF: 0.196

Asia WGS AF: 0.224 AC: 779 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.2
Dann	Benign	0.50

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

Other links and lift over

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