dbSNP rs755622: ENSG00000251357:c.432-567G>C (chr22-23894205-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000433835.3(ENSG00000251357):c.432-567G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 575,612 control chromosomes in the GnomAD database, including 14,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.25 ( 5807 hom., cov: 34)

Exomes 𝑓: 0.19 ( 8518 hom. )

Consequence

ENSG00000251357
ENST00000433835.3 intron

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: -0.948

Variant links:

Genes affected

ENSG00000251357 (HGNC:):

ENSG00000251357 links:

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

MIF-AS1 links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIF-AS1	NR_038911.1 link	n.1697C>G		non_coding_transcript_exon_variant	Exon 3 of 3
MIF	NM_002415.2 link	c.-270G>C		upstream_gene_variant		ENST00000215754.8	NP_002406.1	P14174I4AY87

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENSG00000251357	ENST00000433835.3 link	c.432-567G>C	intron_variant	Intron 4 of 5	5		ENSP00000400325.3	H7C1H1
MIF	ENST00000215754.8 link	c.-270G>C	upstream_gene_variant		1	NM_002415.2	ENSP00000215754.7	P14174
MIF	ENST00000465752.1 link	n.-245G>C	upstream_gene_variant		1
MIF-AS1	ENST00000406213.1 link	n.*221C>G	downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38654

AN:

152146

Hom.:

5790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.410

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.223

GnomAD4 exome

AF:

0.192

AC:

81356

AN:

423348

Hom.:

8518

Cov.:

AF XY:

0.194

AC XY:

43705

AN XY:

225798

show subpopulations

Gnomad4 AFR exome

AF:

0.402

Gnomad4 AMR exome

AF:

0.261

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.212

Gnomad4 SAS exome

AF:

0.230

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.169

Gnomad4 OTH exome

AF:

0.205

GnomAD4 genome

AF:

0.254

AC:

38720

AN:

152264

Hom.:

5807

Cov.:

AF XY:

0.257

AC XY:

19136

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.410

Gnomad4 AMR

AF:

0.262

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.201

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.219

Alfa

AF:

0.227

Hom.:

587

Bravo

AF:

0.259

Asia WGS

AF:

0.252

AC:

877

AN:

3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RHEUMATOID ARTHRITIS, SYSTEMIC JUVENILE, SUSCEPTIBILITY TO

Other:1

May 01, 2003

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.8

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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