Genetic Variant NM_021933.4:c.463-9C>A (chr1-12022824-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021933.4(MIIP):c.463-9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,862 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MIIP
NM_021933.4 intron

Scores

Splicing: ADA: 0.002307

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0350

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MIIP	NM_021933.4 link	c.463-9C>A	intron_variant	Intron 3 of 9	ENST00000235332.6	NP_068752.2	Q5JXC2-1
MIIP	XM_011541895.2 link	c.463-9C>A	intron_variant	Intron 3 of 9		XP_011540197.1	Q5JXC2-1
MIIP	XM_011541896.2 link	c.463-9C>A	intron_variant	Intron 3 of 9		XP_011540198.1	Q5JXC2-1
MIIP	XM_005263487.5 link	c.463-9C>A	intron_variant	Intron 3 of 9		XP_005263544.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MIIP	ENST00000235332.6 link	c.463-9C>A	intron_variant	Intron 3 of 9	1	NM_021933.4	ENSP00000235332.4	Q5JXC2-1
MIIP	ENST00000466860.5 link	n.222-9C>A	intron_variant	Intron 1 of 5	5
MIIP	ENST00000478749.5 link	n.436-9C>A	intron_variant	Intron 2 of 5	2
MIIP	ENST00000498685.5 link	n.-40C>A	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1444862

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717550

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.9

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0023

dbscSNV1_RF

Benign

0.044

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over