Genetic Variant MYO18B:c.39+219G>C (chr22-25761350-G-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_032608.7(MYO18B):c.39+219G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,738 control chromosomes in the GnomAD database, including 4,772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 4772 hom., cov: 32)

Consequence

MYO18B
NM_032608.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.841

Publications

3 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 22-25761350-G-C is Benign according to our data. Variant chr22-25761350-G-C is described in ClinVar as [Benign]. Clinvar id is 1287380.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7 link	c.39+219G>C		intron_variant	Intron 2 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.39+219G>C	intron_variant	Intron 2 of 43	1	NM_032608.7	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6 link	c.39+219G>C	intron_variant	Intron 2 of 43	1		ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5 link	c.39+219G>C	intron_variant	Intron 2 of 42	1		ENSP00000441229.1	Q8IUG5-1
MYO18B	ENST00000539302.5 link	n.39+219G>C	intron_variant	Intron 1 of 41	1		ENSP00000437587.1	F5H6I8

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36880

AN:

151620

Hom.:

4755

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.172

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.247

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.243

AC:

36922

AN:

151738

Hom.:

4772

Cov.:

AF XY:

0.238

AC XY:

17674

AN XY:

74132

show subpopulations

African (AFR)

AF:

0.344

AC:

14180

AN:

41236

American (AMR)

AF:

0.197

AC:

3015

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

984

AN:

3468

East Asian (EAS)

AF:

0.168

AC:

861

AN:

5136

South Asian (SAS)

AF:

0.144

AC:

695

AN:

4810

European-Finnish (FIN)

AF:

0.165

AC:

1741

AN:

10564

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.216

AC:

14692

AN:

67936

Other (OTH)

AF:

0.244

AC:

514

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1436

2873

4309

5746

7182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0611

Hom.:

Bravo

AF:

0.257

Asia WGS

AF:

0.154

AC:

539

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 13, 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

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.41

(source)

DANN

Benign

0.41

PhyloP100

-0.84

Mutation Taster

=100/0

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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22-25761350-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over