rs133885

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032608.7(MYO18B):c.131G>A(p.Gly44Glu) variant causes a missense change. The variant allele was found at a frequency of 0.492 in 1,612,264 control chromosomes in the GnomAD database, including 206,410 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.59 ( 28924 hom., cov: 31)

Exomes 𝑓: 0.48 ( 177486 hom. )

Consequence

MYO18B
NM_032608.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.88

Variant links:

Genes affected

MYO18B (HGNC:18150): (myosin XVIIIB) The protein encoded by this gene may regulate muscle-specific genes when in the nucleus and may influence intracellular trafficking when in the cytoplasm. The encoded protein functions as a homodimer and may interact with F actin. Mutations in this gene are associated with lung cancer. [provided by RefSeq, Jul 2008]

MYO18B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.7819443E-7).

BP6

Variant 22-25763322-G-A is Benign according to our data. Variant chr22-25763322-G-A is described in ClinVar as [Benign]. Clinvar id is 1245085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18B	NM_032608.7 linkuse as main transcript	c.131G>A	p.Gly44Glu	missense_variant	3/44	ENST00000335473.12	NP_115997.5	Q8IUG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYO18B	ENST00000335473.12 linkuse as main transcript	c.131G>A	p.Gly44Glu	missense_variant	3/44	1	NM_032608.7	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6 linkuse as main transcript	c.131G>A	p.Gly44Glu	missense_variant	3/44	1		ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5 linkuse as main transcript	c.131G>A	p.Gly44Glu	missense_variant	3/43	1		ENSP00000441229.1	Q8IUG5-1
MYO18B	ENST00000539302.5 linkuse as main transcript	n.131G>A		non_coding_transcript_exon_variant	2/42	1		ENSP00000437587.1	F5H6I8

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89623

AN:

151890

Hom.:

28850

Cov.:

show subpopulations

Gnomad AFR

AF:

0.842

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.612

Gnomad ASJ

AF:

0.541

Gnomad EAS

AF:

0.825

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.440

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.566

GnomAD3 exomes

AF:

0.549

AC:

135732

AN:

247184

Hom.:

40127

AF XY:

0.535

AC XY:

71840

AN XY:

134212

show subpopulations

Gnomad AFR exome

AF:

0.852

Gnomad AMR exome

AF:

0.719

Gnomad ASJ exome

AF:

0.537

Gnomad EAS exome

AF:

0.822

Gnomad SAS exome

AF:

0.546

Gnomad FIN exome

AF:

0.434

Gnomad NFE exome

AF:

0.439

Gnomad OTH exome

AF:

0.505

GnomAD4 exome

AF:

0.482

AC:

704014

AN:

1460256

Hom.:

177486

Cov.:

AF XY:

0.481

AC XY:

349536

AN XY:

726382

show subpopulations

Gnomad4 AFR exome

AF:

0.861

Gnomad4 AMR exome

AF:

0.707

Gnomad4 ASJ exome

AF:

0.543

Gnomad4 EAS exome

AF:

0.826

Gnomad4 SAS exome

AF:

0.545

Gnomad4 FIN exome

AF:

0.428

Gnomad4 NFE exome

AF:

0.444

Gnomad4 OTH exome

AF:

0.517

GnomAD4 genome

AF:

0.590

AC:

89758

AN:

152008

Hom.:

28924

Cov.:

AF XY:

0.592

AC XY:

44015

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.843

Gnomad4 AMR

AF:

0.612

Gnomad4 ASJ

AF:

0.541

Gnomad4 EAS

AF:

0.826

Gnomad4 SAS

AF:

0.570

Gnomad4 FIN

AF:

0.440

Gnomad4 NFE

AF:

0.446

Gnomad4 OTH

AF:

0.567

Alfa

AF:

0.485

Hom.:

46458

Bravo

AF:

0.619

TwinsUK

AF:

0.420

AC:

1559

ALSPAC

AF:

0.431

AC:

1663

ESP6500AA

AF:

0.845

AC:

3219

ESP6500EA

AF:

0.444

AC:

3665

ExAC

AF:

0.543

AC:

65546

Asia WGS

AF:

0.710

AC:

2469

AN:

3478

EpiCase

AF:

0.454

EpiControl

AF:

0.444

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 17000706) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.53

DEOGEN2

Benign

0.011

T;T;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.25

.;T;T

MetaRNN

Benign

5.8e-7

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.1

N;N;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

3.3

N;N;N

REVEL

Benign

0.19

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Vest4

0.28

MPC

0.082

ClinPred

0.0014

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over