22-23894172-C-T

Variant names:

• chr22-23894172-C-T
• rs9282783
• ENST00000433835.3:c.432-600C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000433835.3(ENSG00000251357):​c.432-600C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 386,904 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: ENSG00000251357 ENST00000433835.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIF-AS1	NR_038911.1		n.1730G>A		non_coding_transcript_exon	Exon 3 of 3
	MIF	NM_002415.2	MANE Select	c.-303C>T		upstream_gene	N/A	NP_002406.1	P14174

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000251357	ENST00000433835.3	TSL:5	c.432-600C>T		intron	N/A	ENSP00000400325.3	H7C1H1
	ENSG00000290199	ENST00000717616.1		n.213-2706G>A		intron	N/A
	MIF	ENST00000215754.8	TSL:1 MANE Select	c.-303C>T		upstream_gene	N/A	ENSP00000215754.7	P14174

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000258 AC: 1 AN: 386904 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 205068

African (AFR) AF: 0.00 AC: 0 AN: 7382

American (AMR) AF: 0.0000763 AC: 1 AN: 13104

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11444

East Asian (EAS) AF: 0.00 AC: 0 AN: 24258

South Asian (SAS) AF: 0.00 AC: 0 AN: 41910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 237416

Other (OTH) AF: 0.00 AC: 0 AN: 22572

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.94
DANN	Benign	0.78
PhyloP100		-2.0
PromoterAI		-0.070	Neutral

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

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

Other links and lift over

dbSNP: rs9282783;

hg19: chr22-24236359;