Genetic Variant MIPOL1:p.Ile159Ile (chr14-37270509-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_001388067.1(MIPOL1):c.477T>C(p.Ile159Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000617 in 1,595,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 0 hom. )

Consequence

MIPOL1
NM_001388067.1 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.72

Publications

0 publications found

Variant links:

Genes affected

MIPOL1 (HGNC:21460): (mirror-image polydactyly 1) This gene encodes a coiled-coil domain-containing protein. The encoded protein may function as a tumor suppressor. A translocation that results in truncation of the protein encoded by this locus has been associated with mirror-image polydactyly, also known as Laurin-Sandrow Syndrome. Alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2010]

MIPOL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 14-37270509-T-C is Benign according to our data. Variant chr14-37270509-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3050985.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.72 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388067.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIPOL1	NM_001388067.1	MANE Select	c.477T>C	p.Ile159Ile	synonymous	Exon 6 of 13	NP_001374996.1	Q8TD10-1
MIPOL1	NM_001388069.1		c.477T>C	p.Ile159Ile	synonymous	Exon 6 of 13	NP_001374998.1	A0A8Q3SHY7
MIPOL1	NM_001195296.2		c.477T>C	p.Ile159Ile	synonymous	Exon 8 of 15	NP_001182225.1	Q8TD10-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIPOL1	ENST00000684589.1	MANE Select	c.477T>C	p.Ile159Ile	synonymous	Exon 6 of 13	ENSP00000506738.1	Q8TD10-1
MIPOL1	ENST00000327441.11	TSL:1	c.477T>C	p.Ile159Ile	synonymous	Exon 7 of 14	ENSP00000333539.7	Q8TD10-1
MIPOL1	ENST00000396294.7	TSL:1	c.477T>C	p.Ile159Ile	synonymous	Exon 8 of 15	ENSP00000379589.2	Q8TD10-1

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000379

AC:

AN:

237308

AF XY:

0.000396

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.0000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000786

Gnomad OTH exome

AF:

0.000353

GnomAD4 exome

AF:

0.000636

AC:

918

AN:

1443234

Hom.:

Cov.:

AF XY:

0.000635

AC XY:

456

AN XY:

718118

show subpopulations

African (AFR)

AF:

0.0000614

AC:

AN:

32576

American (AMR)

AF:

0.0000469

AC:

AN:

42688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25658

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38846

South Asian (SAS)

AF:

0.00

AC:

AN:

83878

European-Finnish (FIN)

AF:

0.0000378

AC:

AN:

52854

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.000803

AC:

884

AN:

1101558

Other (OTH)

AF:

0.000454

AC:

AN:

59500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

116

154

193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<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:

0.000434

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41536

American (AMR)

AF:

0.000131

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000838

AC:

AN:

67996

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000579

Hom.:

Bravo

AF:

0.000431

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MIPOL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.8

(source)

DANN

Benign

0.76

PhyloP100

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

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

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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