Genetic Variant NM_021933.4:c.463-9C>T (chr1-12022824-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021933.4(MIIP):c.463-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,593,424 control chromosomes in the GnomAD database, including 43,525 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 3583 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39942 hom. )

Consequence

MIIP
NM_021933.4 intron

Scores

Splicing: ADA: 0.00002875

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0350

Publications

15 publications found

Variant links:

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]

MIIP links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021933.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIIP	NM_021933.4	MANE Select	c.463-9C>T		intron	N/A	NP_068752.2	Q5JXC2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MIIP	ENST00000235332.6	TSL:1 MANE Select	c.463-9C>T	intron	N/A	ENSP00000235332.4	Q5JXC2-1
MIIP	ENST00000857909.1		c.463-9C>T	intron	N/A	ENSP00000527968.1
MIIP	ENST00000857910.1		c.463-9C>T	intron	N/A	ENSP00000527969.1

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31987

AN:

151992

Hom.:

3584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.0525

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.199

GnomAD2 exomes

AF:

0.197

AC:

44539

AN:

225804

AF XY:

0.200

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.215

Gnomad EAS exome

AF:

0.0505

Gnomad FIN exome

AF:

0.285

Gnomad NFE exome

AF:

0.244

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.229

AC:

330168

AN:

1441314

Hom.:

39942

Cov.:

AF XY:

0.228

AC XY:

163226

AN XY:

715938

show subpopulations

African (AFR)

AF:

0.168

AC:

5542

AN:

33020

American (AMR)

AF:

0.110

AC:

4703

AN:

42822

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

5452

AN:

25792

East Asian (EAS)

AF:

0.0424

AC:

1658

AN:

39078

South Asian (SAS)

AF:

0.168

AC:

14062

AN:

83664

European-Finnish (FIN)

AF:

0.288

AC:

15134

AN:

52480

Middle Eastern (MID)

AF:

0.177

AC:

1011

AN:

5726

European-Non Finnish (NFE)

AF:

0.246

AC:

270290

AN:

1099086

Other (OTH)

AF:

0.206

AC:

12316

AN:

59646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

10848

21697

32545

43394

54242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8974

17948

26922

35896

44870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.210

AC:

32006

AN:

152110

Hom.:

3583

Cov.:

AF XY:

0.209

AC XY:

15536

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.171

AC:

7099

AN:

41514

American (AMR)

AF:

0.139

AC:

2120

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

765

AN:

3472

East Asian (EAS)

AF:

0.0528

AC:

273

AN:

5166

South Asian (SAS)

AF:

0.165

AC:

795

AN:

4822

European-Finnish (FIN)

AF:

0.289

AC:

3049

AN:

10554

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.253

AC:

17185

AN:

67964

Other (OTH)

AF:

0.196

AC:

415

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1325

2650

3975

5300

6625

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.228

Hom.:

14073

Bravo

AF:

0.195

Asia WGS

AF:

0.106

AC:

371

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.4

(source)

DANN

Benign

0.76

PhyloP100

0.035

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000029

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over