Genetic Variant MYO18B:c.4225-33G>C (chr22-25877926-G-C) – 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.4225-33G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,537,184 control chromosomes in the GnomAD database, including 164,693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.44 ( 14898 hom., cov: 32)

Exomes 𝑓: 0.46 ( 149795 hom. )

Consequence

MYO18B
NM_032608.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0300

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:

MYO18B-AS1 (HGNC:40831): (MYO18B antisense RNA 1)

MYO18B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 22-25877926-G-C is Benign according to our data. Variant chr22-25877926-G-C is described in ClinVar as [Benign]. Clinvar id is 1243210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7 link	c.4225-33G>C		intron_variant	Intron 24 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.4225-33G>C	intron_variant	Intron 24 of 43	1	NM_032608.7	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6 link	c.4228-33G>C	intron_variant	Intron 24 of 43	1		ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5 link	c.4225-33G>C	intron_variant	Intron 24 of 42	1		ENSP00000441229.1	Q8IUG5-1
MYO18B	ENST00000539302.5 link	n.*1683-33G>C	intron_variant	Intron 22 of 41	1		ENSP00000437587.1	F5H6I8

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66136

AN:

151946

Hom.:

14889

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.439

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.464

Gnomad OTH

AF:

0.418

GnomAD3 exomes

AF:

0.478

AC:

77637

AN:

162462

Hom.:

19408

AF XY:

0.468

AC XY:

40059

AN XY:

85506

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.667

Gnomad ASJ exome

AF:

0.386

Gnomad EAS exome

AF:

0.431

Gnomad SAS exome

AF:

0.420

Gnomad FIN exome

AF:

0.493

Gnomad NFE exome

AF:

0.466

Gnomad OTH exome

AF:

0.459

GnomAD4 exome

AF:

0.462

AC:

639519

AN:

1385120

Hom.:

149795

Cov.:

AF XY:

0.461

AC XY:

315710

AN XY:

684596

show subpopulations

Gnomad4 AFR exome

AF:

0.313

Gnomad4 AMR exome

AF:

0.653

Gnomad4 ASJ exome

AF:

0.387

Gnomad4 EAS exome

AF:

0.473

Gnomad4 SAS exome

AF:

0.421

Gnomad4 FIN exome

AF:

0.491

Gnomad4 NFE exome

AF:

0.465

Gnomad4 OTH exome

AF:

0.435

GnomAD4 genome

AF:

0.435

AC:

66163

AN:

152064

Hom.:

14898

Cov.:

AF XY:

0.438

AC XY:

32567

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.329

Gnomad4 AMR

AF:

0.569

Gnomad4 ASJ

AF:

0.393

Gnomad4 EAS

AF:

0.439

Gnomad4 SAS

AF:

0.416

Gnomad4 FIN

AF:

0.500

Gnomad4 NFE

AF:

0.464

Gnomad4 OTH

AF:

0.417

Alfa

AF:

0.445

Hom.:

2810

Bravo

AF:

0.436

Asia WGS

AF:

0.442

AC:

1536

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

Nov 12, 2018

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

-0.87

CADD

Benign

1.8

DANN

Benign

0.30

BranchPoint Hunter

0.0

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