22-23895031-C-T

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.282-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,545,302 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (14 hom.)
• Consequence: MIF NM_002415.2 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003961
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.741

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=-0.74).
• BP6: Variant 22-23895031-C-T is Benign according to our data. Variant chr22-23895031-C-T is described in ClinVar as [Benign]. Clinvar id is 781909.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIF	NM_002415.2	c.282-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000215754.8
MIF-AS1	NR_038911.1	n.871G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIF	ENST00000215754.8	c.282-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002415.2	P1
MIF-AS1	ENST00000406213.1	n.871G>A		non_coding_transcript_exon_variant	3/3	1
MIF	ENST00000465752.1	n.393C>T		non_coding_transcript_exon_variant	2/2	1
MIF	ENST00000498385.1	n.248-9C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00540 AC: 822 AN: 152196 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.00956

GnomAD3 exomes AF: 0.00288 AC: 444 AN: 153908 Hom.: 1 AF XY: 0.00269 AC XY: 219 AN XY: 81490

Gnomad AFR exome AF: 0.0146

Gnomad AMR exome AF: 0.00357

Gnomad ASJ exome AF: 0.0140

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00158

Gnomad OTH exome AF: 0.00504

GnomAD4 exome AF: 0.00154 AC: 2147 AN: 1392992 Hom.: 14 Cov.: 34 AF XY: 0.00149 AC XY: 1023 AN XY: 686268

Gnomad4 AFR exome AF: 0.0146

Gnomad4 AMR exome AF: 0.00424

Gnomad4 ASJ exome AF: 0.0138

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000855

Gnomad4 OTH exome AF: 0.00396

GnomAD4 genome AF: 0.00542 AC: 825 AN: 152310 Hom.: 6 Cov.: 33 AF XY: 0.00540 AC XY: 402 AN XY: 74488

Gnomad4 AFR AF: 0.0135

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00286 Hom.: 0

Bravo AF: 0.00620

Asia WGS AF: 0.00202 AC: 7 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 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	4.4
Dann	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000040
dbscSNV1_RF	Benign	0.0020
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: rs189811391; hg19: chr22-24237218;