NM_002415.2:c.282-6C>G

Variant names:

• chr22-23895034-C-G
• rs2070766
• NM_002415.2:c.282-6C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002415.2(MIF):​c.282-6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,545,856 control chromosomes in the GnomAD database, including 24,770 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.18 (2463 hom., cov: 33)
  • Exomes 𝑓: 0.18 (22307 hom.)
• Consequence: MIF NM_002415.2 splice_region, intron
• Scores: Splicing: ADA: 0.0007365
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.27
• Publications: 34 publications found

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]

ENSG00000251357 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 22-23895034-C-G is Benign according to our data. Variant chr22-23895034-C-G is described in ClinVar as Benign. ClinVar VariationId is 3060033.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002415.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIF	NM_002415.2	MANE Select	c.282-6C>G		splice_region intron	N/A	NP_002406.1	P14174
	MIF-AS1	NR_038911.1		n.868G>C		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIF	ENST00000215754.8	TSL:1 MANE Select	c.282-6C>G		splice_region intron	N/A	ENSP00000215754.7	P14174
	ENSG00000251357	ENST00000433835.3	TSL:5	c.605-6C>G		splice_region intron	N/A	ENSP00000400325.3	H7C1H1
	MIF-AS1	ENST00000406213.1	TSL:1	n.868G>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26601 AN: 152042 Hom.: 2458 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.163

GnomAD2 exomes AF: 0.194 AC: 30212 AN: 155428 AF XY: 0.192

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.270

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.207

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.189

GnomAD4 exome AF: 0.176 AC: 245858 AN: 1393700 Hom.: 22307 Cov.: 35 AF XY: 0.177 AC XY: 121390 AN XY: 686648

African (AFR) AF: 0.140 AC: 4448 AN: 31696

American (AMR) AF: 0.258 AC: 9277 AN: 35930

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3412 AN: 24392

East Asian (EAS) AF: 0.197 AC: 7079 AN: 35910

South Asian (SAS) AF: 0.203 AC: 15813 AN: 78082

European-Finnish (FIN) AF: 0.228 AC: 11163 AN: 48938

Middle Eastern (MID) AF: 0.159 AC: 841 AN: 5296

European-Non Finnish (NFE) AF: 0.171 AC: 183686 AN: 1075818

Other (OTH) AF: 0.176 AC: 10139 AN: 57638

GnomAD4 genome AF: 0.175 AC: 26628 AN: 152156 Hom.: 2463 Cov.: 33 AF XY: 0.180 AC XY: 13400 AN XY: 74370

African (AFR) AF: 0.143 AC: 5953 AN: 41532

American (AMR) AF: 0.226 AC: 3457 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1013 AN: 5158

South Asian (SAS) AF: 0.202 AC: 973 AN: 4814

European-Finnish (FIN) AF: 0.229 AC: 2423 AN: 10602

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11793 AN: 67966

Other (OTH) AF: 0.160 AC: 337 AN: 2106

Alfa AF: 0.134 Hom.: 493

Bravo AF: 0.171

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MIF-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.6
DANN	Benign	0.75
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00074
dbscSNV1_RF	Benign	0.028
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2070766;

hg19: chr22-24237221;

COSMIC: COSV53158996;