22-23895033-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002415.2(MIF):c.282-7C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000862 in 1,546,016 control chromosomes in the GnomAD database, including 6 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00056 (3 hom.)
• Consequence: MIF NM_002415.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0009606
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0560

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 22-23895033-C-A is Benign according to our data. Variant chr22-23895033-C-A is described in ClinVar as [Benign]. Clinvar id is 712657.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIF	NM_002415.2	c.282-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000215754.8
MIF-AS1	NR_038911.1	n.869G>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIF	ENST00000215754.8	c.282-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002415.2	P1
MIF-AS1	ENST00000406213.1	n.869G>T		non_coding_transcript_exon_variant	3/3	1
MIF	ENST00000465752.1	n.395C>A		non_coding_transcript_exon_variant	2/2	1
MIF	ENST00000498385.1	n.248-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00365 AC: 555 AN: 152170 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00131 AC: 204 AN: 155290 Hom.: 3 AF XY: 0.00120 AC XY: 99 AN XY: 82216

Gnomad AFR exome AF: 0.0124

Gnomad AMR exome AF: 0.00267

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000266

Gnomad OTH exome AF: 0.00159

GnomAD4 exome AF: 0.000557 AC: 777 AN: 1393732 Hom.: 3 Cov.: 34 AF XY: 0.000481 AC XY: 330 AN XY: 686708

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.00273

Gnomad4 ASJ exome AF: 0.0000820

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000256

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000190

Gnomad4 OTH exome AF: 0.00154

GnomAD4 genome AF: 0.00364 AC: 555 AN: 152284 Hom.: 3 Cov.: 33 AF XY: 0.00369 AC XY: 275 AN XY: 74470

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00162 Hom.: 3

Bravo AF: 0.00472

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	5.4
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00096
dbscSNV1_RF	Benign	0.066
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

Publications

LitVar

Other links and lift over

dbSNP: rs35625249; hg19: chr22-24237220;