chr1-12021838-G-A

Position:

• chr1-12021838-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021933.4(MIIP):​c.112G>A​(p.Glu38Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 1,604,204 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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 0.0025 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (136 hom.)
• Consequence: MIIP NM_021933.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001130
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0440

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002331376).
• BP6: Variant 1-12021838-G-A is Benign according to our data. Variant chr1-12021838-G-A is described in ClinVar as [Benign]. Clinvar id is 713174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.068 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIIP	NM_021933.4	c.112G>A	p.Glu38Lys	missense_variant, splice_region_variant	2/10	ENST00000235332.6	NP_068752.2
MIIP	XM_011541895.2	c.112G>A	p.Glu38Lys	missense_variant, splice_region_variant	2/10		XP_011540197.1
MIIP	XM_011541896.2	c.112G>A	p.Glu38Lys	missense_variant, splice_region_variant	2/10		XP_011540198.1
MIIP	XM_005263487.5	c.112G>A	p.Glu38Lys	missense_variant, splice_region_variant	2/10		XP_005263544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIIP	ENST00000235332.6	c.112G>A	p.Glu38Lys	missense_variant, splice_region_variant	2/10	1	NM_021933.4	ENSP00000235332	P1
MIIP	ENST00000478749.5	n.88-257G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00257 AC: 391 AN: 152238 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0475

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00435 AC: 1031 AN: 237148 Hom.: 16 AF XY: 0.00393 AC XY: 507 AN XY: 128990

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00528

Gnomad ASJ exome AF: 0.000212

Gnomad EAS exome AF: 0.0406

Gnomad SAS exome AF: 0.00200

Gnomad FIN exome AF: 0.000114

Gnomad NFE exome AF: 0.000288

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00256 AC: 3719 AN: 1451848 Hom.: 136 Cov.: 31 AF XY: 0.00254 AC XY: 1830 AN XY: 721866

Gnomad4 AFR exome AF: 0.000180

Gnomad4 AMR exome AF: 0.00623

Gnomad4 ASJ exome AF: 0.000272

Gnomad4 EAS exome AF: 0.0702

Gnomad4 SAS exome AF: 0.00215

Gnomad4 FIN exome AF: 0.000260

Gnomad4 NFE exome AF: 0.000234

Gnomad4 OTH exome AF: 0.00318

GnomAD4 genome AF: 0.00255 AC: 388 AN: 152356 Hom.: 6 Cov.: 32 AF XY: 0.00281 AC XY: 209 AN XY: 74506

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0474

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00253 Hom.: 6

Bravo AF: 0.00243

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00392 AC: 475

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 18, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.0
DANN	Benign	0.95
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.79	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.033
Sift	Benign	0.30	T
Sift4G	Benign	0.64	T
Polyphen		0.037	B
Vest4		0.11
MVP		0.10
MPC		0.15
ClinPred		0.0019	T
GERP RS		0.84
Varity_R		0.058
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.0
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

Publications

LitVar

Other links and lift over

dbSNP: rs117242156; hg19: chr1-12081895; COSMIC: COSV52427538; COSMIC: COSV52427538;