rs11588779

Positions:

• chr1-12022824-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021933.4(MIIP):​c.463-9C>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002875
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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 (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/exons	MANE	Protein	UniProt
MIIP	NM_021933.4	c.463-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000235332.6	NP_068752.2
MIIP	XM_005263487.5	c.463-9C>T		splice_polypyrimidine_tract_variant, intron_variant			XP_005263544.1
MIIP	XM_011541895.2	c.463-9C>T		splice_polypyrimidine_tract_variant, intron_variant			XP_011540197.1
MIIP	XM_011541896.2	c.463-9C>T		splice_polypyrimidine_tract_variant, intron_variant			XP_011540198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIIP	ENST00000235332.6	c.463-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_021933.4	ENSP00000235332	P1
MIIP	ENST00000466860.5	n.222-9C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5
MIIP	ENST00000478749.5	n.436-9C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2
MIIP	ENST00000498685.5			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

GnomAD3 exomes AF: 0.197 AC: 44539 AN: 225804 Hom.: 4947 AF XY: 0.200 AC XY: 24349 AN XY: 121756

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 SAS exome AF: 0.170

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

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.0424

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.206

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

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.0528

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.196

Alfa AF: 0.233 Hom.: 9964

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

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

LitVar

Other links and lift over

dbSNP: rs11588779; hg19: chr1-12082881;