chr22-25761101-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032608.7(MYO18B):c.9C>G(p.Ile3Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,612,852 control chromosomes in the GnomAD database, including 26,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1737 hom., cov: 33)

Exomes 𝑓: 0.18 ( 24495 hom. )

Consequence

MYO18B
NM_032608.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.175

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, ClinGen, G2P

MYO18B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016304553).

BP6

Variant 22-25761101-C-G is Benign according to our data. Variant chr22-25761101-C-G is described in ClinVar as [Benign]. Clinvar id is 1321829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7 link	c.9C>G	p.Ile3Met	missense_variant	Exon 2 of 44	ENST00000335473.12	NP_115997.5	Q8IUG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO18B	ENST00000335473.12 link	c.9C>G	p.Ile3Met	missense_variant	Exon 2 of 44	1	NM_032608.7	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6 link	c.9C>G	p.Ile3Met	missense_variant	Exon 2 of 44	1		ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5 link	c.9C>G	p.Ile3Met	missense_variant	Exon 2 of 43	1		ENSP00000441229.1	Q8IUG5-1
MYO18B	ENST00000539302.5 link	n.9C>G		non_coding_transcript_exon_variant	Exon 1 of 42	1		ENSP00000437587.1	F5H6I8

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20030

AN:

152148

Hom.:

1737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0395

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.148

GnomAD2 exomes

AF:

0.142

AC:

35447

AN:

248832

AF XY:

0.147

show subpopulations

Gnomad AFR exome

AF:

0.0352

Gnomad AMR exome

AF:

0.0891

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.000667

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.195

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.176

AC:

256892

AN:

1460586

Hom.:

24495

Cov.:

AF XY:

0.175

AC XY:

127181

AN XY:

726634

show subpopulations

African (AFR)

AF:

0.0343

AC:

1149

AN:

33478

American (AMR)

AF:

0.0928

AC:

4150

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

6488

AN:

26126

East Asian (EAS)

AF:

0.000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.110

AC:

9513

AN:

86222

European-Finnish (FIN)

AF:

0.145

AC:

7649

AN:

52898

Middle Eastern (MID)

AF:

0.213

AC:

1228

AN:

5768

European-Non Finnish (NFE)

AF:

0.195

AC:

216869

AN:

1111342

Other (OTH)

AF:

0.163

AC:

9826

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

11146

22293

33439

44586

55732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.132

AC:

20025

AN:

152266

Hom.:

1737

Cov.:

AF XY:

0.129

AC XY:

9588

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0393

AC:

1636

AN:

41578

American (AMR)

AF:

0.112

AC:

1715

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

881

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.105

AC:

508

AN:

4826

European-Finnish (FIN)

AF:

0.146

AC:

1551

AN:

10596

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.195

AC:

13232

AN:

68002

Other (OTH)

AF:

0.146

AC:

309

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

921

1841

2762

3682

4603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.184

Hom.:

2096

Bravo

AF:

0.126

TwinsUK

AF:

0.192

AC:

713

ALSPAC

AF:

0.178

AC:

687

ESP6500AA

AF:

0.0403

AC:

177

ESP6500EA

AF:

0.189

AC:

1622

ExAC

AF:

0.141

AC:

17150

Asia WGS

AF:

0.0430

AC:

152

AN:

3478

EpiCase

AF:

0.202

EpiControl

AF:

0.204

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.046

T;T;.

Eigen

Benign

0.077

Eigen_PC

Benign

-0.012

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.77

.;T;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.0

M;M;M

PhyloP100

0.17

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.1

N;N;N

REVEL

Uncertain

0.37

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.28

MPC

0.14

ClinPred

0.063

GERP RS

-0.90

Varity_R

0.21

gMVP

0.14

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr22-25761101-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over