dbSNP rs5752205: MYO18B:c.2312+119G>A (chr22-25781953-G-A) – ACMG Classification: Benign (-20 pts)

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.2312+119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00871 in 651,984 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 89 hom., cov: 33)

Exomes 𝑓: 0.0051 ( 63 hom. )

Consequence

MYO18B
NM_032608.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.830

Publications

1 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 (BayesDel_noAF=-0.85).

BP6

Variant 22-25781953-G-A is Benign according to our data. Variant chr22-25781953-G-A is described in ClinVar as Benign. ClinVar VariationId is 1183853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.063 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7 link	c.2312+119G>A		intron_variant	Intron 10 of 43	ENST00000335473.12	NP_115997.5	Q8IUG5-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO18B	ENST00000335473.12 link	c.2312+119G>A	intron_variant	Intron 10 of 43	1	NM_032608.7	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6 link	c.2312+119G>A	intron_variant	Intron 10 of 43	1		ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5 link	c.2312+119G>A	intron_variant	Intron 10 of 42	1		ENSP00000441229.1	Q8IUG5-1
MYO18B	ENST00000539302.5 link	n.2312+119G>A	intron_variant	Intron 9 of 41	1		ENSP00000437587.1	F5H6I8

Frequencies

GnomAD3 genomes

AF:

0.0207

AC:

3143

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00838

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0384

Gnomad SAS

AF:

0.0103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0139

GnomAD4 exome

AF:

0.00505

AC:

2524

AN:

499666

Hom.:

AF XY:

0.00489

AC XY:

1234

AN XY:

252212

show subpopulations

African (AFR)

AF:

0.0698

AC:

852

AN:

12200

American (AMR)

AF:

0.00621

AC:

AN:

10468

Ashkenazi Jewish (ASJ)

AF:

0.000336

AC:

AN:

11892

East Asian (EAS)

AF:

0.0336

AC:

855

AN:

25426

South Asian (SAS)

AF:

0.0115

AC:

255

AN:

22106

European-Finnish (FIN)

AF:

0.000152

AC:

AN:

26282

Middle Eastern (MID)

AF:

0.00587

AC:

AN:

2044

European-Non Finnish (NFE)

AF:

0.000580

AC:

211

AN:

363880

Other (OTH)

AF:

0.0105

AC:

266

AN:

25368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

122

244

367

489

611

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.0207

AC:

3152

AN:

152318

Hom.:

Cov.:

AF XY:

0.0207

AC XY:

1540

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0651

AC:

2703

AN:

41546

American (AMR)

AF:

0.00836

AC:

128

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.0385

AC:

200

AN:

5190

South Asian (SAS)

AF:

0.0103

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

68030

Other (OTH)

AF:

0.0137

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

160

320

479

639

799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0142

Hom.:

Bravo

AF:

0.0235

Asia WGS

AF:

0.0290

AC:

102

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.3

(source)

DANN

Benign

0.77

PhyloP100

0.83

Mutation Taster

=100/0

polymorphism

(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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over