1-12022869-A-G

Position:

• chr1-12022869-A-G

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MIIP	NM_021933.4	c.499A>G	p.Lys167Glu	missense_variant	4/10	ENST00000235332.6	NP_068752.2
MIIP	XM_011541895.2	c.499A>G	p.Lys167Glu	missense_variant	4/10		XP_011540197.1
MIIP	XM_011541896.2	c.499A>G	p.Lys167Glu	missense_variant	4/10		XP_011540198.1
MIIP	XM_005263487.5	c.499A>G	p.Lys167Glu	missense_variant	4/10		XP_005263544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIIP	ENST00000235332.6	c.499A>G	p.Lys167Glu	missense_variant	4/10	1	NM_021933.4	ENSP00000235332	P1
MIIP	ENST00000466860.5	n.258A>G		non_coding_transcript_exon_variant	2/6	5
MIIP	ENST00000478749.5	n.472A>G		non_coding_transcript_exon_variant	3/6	2
MIIP	ENST00000498685.5	n.6A>G		non_coding_transcript_exon_variant	1/6	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

GnomAD3 exomes AF: 0.682 AC: 165360 AN: 242416 Hom.: 57370 AF XY: 0.681 AC XY: 89221 AN XY: 130948

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 SAS exome AF: 0.628

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

Gnomad4 AFR exome AF: 0.785

Gnomad4 AMR exome AF: 0.576

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.502

Gnomad4 SAS exome AF: 0.633

Gnomad4 FIN exome AF: 0.820

Gnomad4 NFE exome AF: 0.716

Gnomad4 OTH exome AF: 0.697

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

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.702

Alfa AF: 0.704 Hom.: 96005

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
MutationTaster	Benign	1.0	P;P
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

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs2295283; hg19: chr1-12082926; COSMIC: COSV52427147; COSMIC: COSV52427147;