rs9624909

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.2774C>T(p.Ser925Leu) variant causes a missense change. The variant allele was found at a frequency of 0.212 in 1,612,254 control chromosomes in the GnomAD database, including 38,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3373 hom., cov: 32)

Exomes 𝑓: 0.21 ( 35295 hom. )

Consequence

MYO18B
NM_032608.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.62

Publications

15 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=0.0018035173).

BP6

Variant 22-25826487-C-T is Benign according to our data. Variant chr22-25826487-C-T is described in CliVar as Benign. Clinvar id is 1273583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-25826487-C-T is described in CliVar as Benign. Clinvar id is 1273583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-25826487-C-T is described in CliVar as Benign. Clinvar id is 1273583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-25826487-C-T is described in CliVar as Benign. Clinvar id is 1273583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-25826487-C-T is described in CliVar as Benign. Clinvar id is 1273583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7 link	c.2774C>T	p.Ser925Leu	missense_variant	Exon 14 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.2774C>T	p.Ser925Leu	missense_variant	Exon 14 of 44	1	NM_032608.7	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6 link	c.2774C>T	p.Ser925Leu	missense_variant	Exon 14 of 44	1		ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5 link	c.2774C>T	p.Ser925Leu	missense_variant	Exon 14 of 43	1		ENSP00000441229.1	Q8IUG5-1
MYO18B	ENST00000539302.5 link	n.*232C>T		non_coding_transcript_exon_variant	Exon 12 of 42	1		ENSP00000437587.1	F5H6I8
MYO18B	ENST00000539302.5 link	n.*232C>T		3_prime_UTR_variant	Exon 12 of 42	1		ENSP00000437587.1	F5H6I8

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31280

AN:

152034

Hom.:

3367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.210

GnomAD2 exomes

AF:

0.184

AC:

45794

AN:

248730

AF XY:

0.184

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.00267

Gnomad FIN exome

AF:

0.276

Gnomad NFE exome

AF:

0.226

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.213

AC:

310438

AN:

1460100

Hom.:

35295

Cov.:

AF XY:

0.210

AC XY:

152738

AN XY:

726354

show subpopulations

African (AFR)

AF:

0.198

AC:

6630

AN:

33454

American (AMR)

AF:

0.128

AC:

5714

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

5133

AN:

26084

East Asian (EAS)

AF:

0.00128

AC:

AN:

39690

South Asian (SAS)

AF:

0.125

AC:

10747

AN:

86136

European-Finnish (FIN)

AF:

0.275

AC:

14647

AN:

53340

Middle Eastern (MID)

AF:

0.215

AC:

1236

AN:

5760

European-Non Finnish (NFE)

AF:

0.229

AC:

254303

AN:

1110690

Other (OTH)

AF:

0.199

AC:

11977

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

11331

22661

33992

45322

56653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8552

17104

25656

34208

42760

<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:

0.206

AC:

31300

AN:

152154

Hom.:

3373

Cov.:

AF XY:

0.206

AC XY:

15289

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.199

AC:

8259

AN:

41506

American (AMR)

AF:

0.184

AC:

2806

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

678

AN:

3470

East Asian (EAS)

AF:

0.00271

AC:

AN:

5174

South Asian (SAS)

AF:

0.105

AC:

509

AN:

4828

European-Finnish (FIN)

AF:

0.281

AC:

2975

AN:

10576

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15265

AN:

67996

Other (OTH)

AF:

0.207

AC:

437

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1243

2487

3730

4974

6217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.214

Hom.:

17452

Bravo

AF:

0.202

TwinsUK

AF:

0.248

AC:

920

ALSPAC

AF:

0.221

AC:

852

ESP6500AA

AF:

0.189

AC:

741

ESP6500EA

AF:

0.217

AC:

1803

ExAC

AF:

0.185

AC:

22314

Asia WGS

AF:

0.0610

AC:

212

AN:

3478

EpiCase

AF:

0.231

EpiControl

AF:

0.228

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

T;T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

.;D;D

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.3

MutationAssessor

Uncertain

2.5

M;M;M

PhyloP100

4.6

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Pathogenic

0.66

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.98

D;D;.

Vest4

0.24

MPC

0.36

ClinPred

0.032

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.56

gMVP

0.47

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over