Variant 22-23895033-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002415.2(MIF):c.282-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000862 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, intron

Scores

Splicing: ADA: 0.0009606

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0560

Variant links:

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 links:

ENSG00000251357 (HGNC:):

ENSG00000251357 links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIF	NM_002415.2 linkuse as main transcript	c.282-7C>A		splice_region_variant, intron_variant		ENST00000215754.8	NP_002406.1	P14174I4AY87
MIF-AS1	NR_038911.1 linkuse as main transcript	n.869G>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIF	ENST00000215754.8 linkuse as main transcript	c.282-7C>A		splice_region_variant, intron_variant		1	NM_002415.2	ENSP00000215754.7		P14174
ENSG00000251357	ENST00000433835.3 linkuse as main transcript	c.605-7C>A		splice_region_variant, intron_variant		5		ENSP00000400325.3		H7C1H1

Frequencies

GnomAD3 genomes

AF:

0.00365

AC:

555

AN:

152170

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00120

AC XY:

AN XY:

82216

show subpopulations

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.:

Cov.:

AF XY:

0.000481

AC XY:

330

AN XY:

686708

show subpopulations

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.:

Cov.:

AF XY:

0.00369

AC XY:

275

AN XY:

74470

show subpopulations

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.:

Bravo

AF:

0.00472

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2018

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over