chr1-12022824-C-T

Variant names:

• chr1-12022824-C-T
• rs11588779
• NM_021933.4:c.463-9C>T

Variant summary

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

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

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 (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIIP	NM_021933.4	c.463-9C>T		intron_variant	Intron 3 of 9	ENST00000235332.6	NP_068752.2
MIIP	XM_011541895.2	c.463-9C>T		intron_variant	Intron 3 of 9		XP_011540197.1
MIIP	XM_011541896.2	c.463-9C>T		intron_variant	Intron 3 of 9		XP_011540198.1
MIIP	XM_005263487.5	c.463-9C>T		intron_variant	Intron 3 of 9		XP_005263544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIIP	ENST00000235332.6	c.463-9C>T		intron_variant	Intron 3 of 9	1	NM_021933.4	ENSP00000235332.4
MIIP	ENST00000466860.5	n.222-9C>T		intron_variant	Intron 1 of 5	5
MIIP	ENST00000478749.5	n.436-9C>T		intron_variant	Intron 2 of 5	2
MIIP	ENST00000498685.5	n.-40C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31987 AN: 151992 Hom.: 3584 Cov.: 32

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

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.: 29 AF XY: 0.228 AC XY: 163226 AN XY: 715938

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

GnomAD4 genome AF: 0.210 AC: 32006 AN: 152110 Hom.: 3583 Cov.: 32 AF XY: 0.209 AC XY: 15536 AN XY: 74336

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: 49 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17185 AN: 67964

Other (OTH) AF: 0.196 AC: 415 AN: 2112

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.4
DANN	Benign	0.76
PhyloP100		0.035
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11588779; hg19: chr1-12082881;