Genetic Variant MYO18B:c.39+201T>C (chr22-25761332-T-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+201T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 137,652 control chromosomes in the GnomAD database, including 4,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.27 ( 4776 hom., cov: 32)

Consequence

MYO18B
NM_032608.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0520

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:

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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=-0.91).

BP6

Variant 22-25761332-T-C is Benign according to our data. Variant chr22-25761332-T-C is described in ClinVar as [Benign]. Clinvar id is 1291686.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7 link	c.39+201T>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+201T>C	intron_variant	Intron 2 of 43	1	NM_032608.7	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6 link	c.39+201T>C	intron_variant	Intron 2 of 43	1		ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5 link	c.39+201T>C	intron_variant	Intron 2 of 42	1		ENSP00000441229.1	Q8IUG5-1
MYO18B	ENST00000539302.5 link	n.39+201T>C	intron_variant	Intron 1 of 41	1		ENSP00000437587.1	F5H6I8

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

36902

AN:

137578

Hom.:

4759

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.262

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.272

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

GnomAD4 genome

AF:

0.268

AC:

36944

AN:

137652

Hom.:

4776

Cov.:

AF XY:

0.265

AC XY:

17694

AN XY:

66768

show subpopulations

African (AFR)

AF:

0.398

AC:

14186

AN:

35656

American (AMR)

AF:

0.233

AC:

3020

AN:

12942

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

984

AN:

3320

East Asian (EAS)

AF:

0.262

AC:

862

AN:

3286

South Asian (SAS)

AF:

0.172

AC:

694

AN:

4036

European-Finnish (FIN)

AF:

0.175

AC:

1743

AN:

9938

Middle Eastern (MID)

AF:

0.294

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.225

AC:

14701

AN:

65380

Other (OTH)

AF:

0.270

AC:

515

AN:

1908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1474

2947

4421

5894

7368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.229

Hom.:

5648

Bravo

AF:

0.257

Asia WGS

AF:

0.155

AC:

539

AN:

3472

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

-0.91

CADD

Benign

0.54

(source)

DANN

Benign

0.38

PhyloP100

0.052

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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chr22-25761332-T-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