Genetic Variant MOB1B:p.Leu4Leu (chr4-70902548-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_173468.4(MOB1B):c.12G>A(p.Leu4Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MOB1B
NM_173468.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0001436

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

Publications

0 publications found

Variant links:

Genes affected

MOB1B (HGNC:29801): (MOB kinase activator 1B) The protein encoded by this gene is similar to the yeast Mob1 protein. Yeast Mob1 binds Mps1p, a protein kinase essential for spindle pole body duplication and mitotic checkpoint regulation. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

MOB1B links:

ENSG00000289019 (HGNC:58808):

ENSG00000289019 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP7

Synonymous conserved (PhyloP=1.25 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173468.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MOB1B	NM_173468.4	MANE Select	c.12G>A	p.Leu4Leu	splice_region synonymous	Exon 1 of 6	NP_775739.1	Q7L9L4-1
MOB1B	NM_001244766.2		c.-86G>A		splice_region	Exon 1 of 7	NP_001231695.1	Q7L9L4-2
MOB1B	NM_001244767.2		c.12G>A	p.Leu4Leu	splice_region synonymous	Exon 1 of 4	NP_001231696.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MOB1B	ENST00000309395.7	TSL:1 MANE Select	c.12G>A	p.Leu4Leu	splice_region synonymous	Exon 1 of 6	ENSP00000310189.3	Q7L9L4-1
MOB1B	ENST00000396051.2	TSL:2	c.-86G>A		splice_region	Exon 1 of 7	ENSP00000379366.2	Q7L9L4-2
MOB1B	ENST00000502869.5	TSL:3	c.-146G>A		splice_region	Exon 1 of 6	ENSP00000427216.1	D6RCK3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1410736

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

697504

African (AFR)

AF:

0.00

AC:

AN:

32382

American (AMR)

AF:

0.00

AC:

AN:

37852

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25256

East Asian (EAS)

AF:

0.00

AC:

AN:

37170

South Asian (SAS)

AF:

0.00

AC:

AN:

80396

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1087214

Other (OTH)

AF:

0.00

AC:

AN:

58524

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

1.3

PromoterAI

-0.080

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over