1-12022869-A-G

Variant names:

• chr1-12022869-A-G
• rs2295283
• NM_021933.4:c.499A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021933.4(MIIP):​c.499A>G​(p.Lys167Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 1,607,932 control chromosomes in the GnomAD database, including 403,825 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.72 (40164 hom., cov: 30)
  • Exomes 𝑓: 0.70 (363661 hom.)
• Consequence: MIIP NM_021933.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• Publications: 53 publications found

Genes affected

MIIP (HGNC:25715): (migration and invasion inhibitory protein) This gene encodes a protein that interacts with the oncogene protein insulin-like growth factor binding protein 2 and may function as an inhibitor of cell migration and invasion. This protein also interacts with the cell division protein 20 and may be involved in regulating mitotic progression. This protein may function as a tumor suppressor by inhibiting the growth or certain cancers. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.370722E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIIP	NM_021933.4	c.499A>G	p.Lys167Glu	missense_variant	Exon 4 of 10	ENST00000235332.6	NP_068752.2
MIIP	XM_011541895.2	c.499A>G	p.Lys167Glu	missense_variant	Exon 4 of 10		XP_011540197.1
MIIP	XM_011541896.2	c.499A>G	p.Lys167Glu	missense_variant	Exon 4 of 10		XP_011540198.1
MIIP	XM_005263487.5	c.499A>G	p.Lys167Glu	missense_variant	Exon 4 of 10		XP_005263544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIIP	ENST00000235332.6	c.499A>G	p.Lys167Glu	missense_variant	Exon 4 of 10	1	NM_021933.4	ENSP00000235332.4
MIIP	ENST00000466860.5	n.258A>G		non_coding_transcript_exon_variant	Exon 2 of 6	5
MIIP	ENST00000478749.5	n.472A>G		non_coding_transcript_exon_variant	Exon 3 of 6	2
MIIP	ENST00000498685.5	n.6A>G		non_coding_transcript_exon_variant	Exon 1 of 6	2

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109616 AN: 151866 Hom.: 40125 Cov.: 30

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.703

GnomAD2 exomes AF: 0.682 AC: 165360 AN: 242416 AF XY: 0.681

Gnomad AFR exome AF: 0.792

Gnomad AMR exome AF: 0.567

Gnomad ASJ exome AF: 0.609

Gnomad EAS exome AF: 0.552

Gnomad FIN exome AF: 0.823

Gnomad NFE exome AF: 0.718

Gnomad OTH exome AF: 0.689

GnomAD4 exome AF: 0.704 AC: 1024873 AN: 1455948 Hom.: 363661 Cov.: 46 AF XY: 0.702 AC XY: 508047 AN XY: 723830

African (AFR) AF: 0.785 AC: 26188 AN: 33380

American (AMR) AF: 0.576 AC: 25388 AN: 44094

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 15777 AN: 26010

East Asian (EAS) AF: 0.502 AC: 19857 AN: 39522

South Asian (SAS) AF: 0.633 AC: 53939 AN: 85160

European-Finnish (FIN) AF: 0.820 AC: 43519 AN: 53094

Middle Eastern (MID) AF: 0.715 AC: 4119 AN: 5762

European-Non Finnish (NFE) AF: 0.716 AC: 794120 AN: 1108744

Other (OTH) AF: 0.697 AC: 41966 AN: 60182

GnomAD4 genome AF: 0.722 AC: 109722 AN: 151984 Hom.: 40164 Cov.: 30 AF XY: 0.721 AC XY: 53561 AN XY: 74294

African (AFR) AF: 0.786 AC: 32548 AN: 41434

American (AMR) AF: 0.603 AC: 9198 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2099 AN: 3472

East Asian (EAS) AF: 0.552 AC: 2850 AN: 5160

South Asian (SAS) AF: 0.632 AC: 3046 AN: 4818

European-Finnish (FIN) AF: 0.826 AC: 8732 AN: 10572

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.721 AC: 48985 AN: 67960

Other (OTH) AF: 0.702 AC: 1476 AN: 2104

Alfa AF: 0.709 Hom.: 189674

Bravo AF: 0.708

TwinsUK AF: 0.716 AC: 2654

ALSPAC AF: 0.715 AC: 2755

ESP6500AA AF: 0.785 AC: 3459

ESP6500EA AF: 0.714 AC: 6143

ExAC AF: 0.684 AC: 82955

Asia WGS AF: 0.596 AC: 2076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.73
DEOGEN2	Benign	0.00049	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0064	N
LIST_S2	Benign	0.11	T
MetaRNN	Benign	9.4e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
PhyloP100		2.4
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.049
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0030
MPC		0.13
ClinPred		0.00025	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.032
gMVP		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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

Other links and lift over

dbSNP: rs2295283; hg19: chr1-12082926; COSMIC: COSV52427147; COSMIC: COSV52427147;