Genetic Variant MYO18B:c.40-288C>G (chr22-25762943-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032608.7(MYO18B):c.40-288C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 576,634 control chromosomes in the GnomAD database, including 29,282 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8129 hom., cov: 33)

Exomes 𝑓: 0.29 ( 21153 hom. )

Consequence

MYO18B
NM_032608.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.497

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 22-25762943-C-G is Benign according to our data. Variant chr22-25762943-C-G is described in ClinVar as [Benign]. Clinvar id is 1281393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7 link	c.40-288C>G		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.40-288C>G	intron_variant	Intron 2 of 43	1	NM_032608.7	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6 link	c.40-288C>G	intron_variant	Intron 2 of 43	1		ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5 link	c.40-288C>G	intron_variant	Intron 2 of 42	1		ENSP00000441229.1	Q8IUG5-1
MYO18B	ENST00000539302.5 link	n.40-288C>G	intron_variant	Intron 1 of 41	1		ENSP00000437587.1	F5H6I8

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46226

AN:

152036

Hom.:

8105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.645

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.278

GnomAD4 exome

AF:

0.286

AC:

121567

AN:

424480

Hom.:

21153

AF XY:

0.286

AC XY:

67309

AN XY:

235636

show subpopulations

Gnomad4 AFR exome

AF:

0.397

Gnomad4 AMR exome

AF:

0.485

Gnomad4 ASJ exome

AF:

0.233

Gnomad4 EAS exome

AF:

0.655

Gnomad4 SAS exome

AF:

0.374

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.201

Gnomad4 OTH exome

AF:

0.273

GnomAD4 genome

AF:

0.304

AC:

46287

AN:

152154

Hom.:

8129

Cov.:

AF XY:

0.312

AC XY:

23208

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.396

Gnomad4 AMR

AF:

0.382

Gnomad4 ASJ

AF:

0.233

Gnomad4 EAS

AF:

0.645

Gnomad4 SAS

AF:

0.395

Gnomad4 FIN

AF:

0.273

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.284

Alfa

AF:

0.144

Hom.:

263

Bravo

AF:

0.315

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Jun 19, 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

-0.82

CADD

Benign

3.2

DANN

Benign

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over