Genetic Variant MYO18B:c.39+46A>G (chr22-25761177-A-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.39+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,606,262 control chromosomes in the GnomAD database, including 34,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3296 hom., cov: 33)

Exomes 𝑓: 0.21 ( 31510 hom. )

Consequence

MYO18B
NM_032608.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.114

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=-0.91).

BP6

Variant 22-25761177-A-G is Benign according to our data. Variant chr22-25761177-A-G is described in ClinVar as [Benign]. Clinvar id is 1279814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7 link	c.39+46A>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.39+46A>G	intron_variant	Intron 2 of 43	1	NM_032608.7	ENSP00000334563.8	Q8IUG5-1
MYO18B	ENST00000407587.6 link	c.39+46A>G	intron_variant	Intron 2 of 43	1		ENSP00000386096.2	Q8IUG5-3
MYO18B	ENST00000536101.5 link	c.39+46A>G	intron_variant	Intron 2 of 42	1		ENSP00000441229.1	Q8IUG5-1
MYO18B	ENST00000539302.5 link	n.39+46A>G	intron_variant	Intron 1 of 41	1		ENSP00000437587.1	F5H6I8

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31282

AN:

151960

Hom.:

3285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.211

GnomAD3 exomes

AF:

0.194

AC:

47490

AN:

245252

Hom.:

4808

AF XY:

0.192

AC XY:

25556

AN XY:

133364

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.121

Gnomad SAS exome

AF:

0.132

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.206

AC:

298989

AN:

1454184

Hom.:

31510

Cov.:

AF XY:

0.204

AC XY:

147541

AN XY:

723792

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.198

Gnomad4 ASJ exome

AF:

0.260

Gnomad4 EAS exome

AF:

0.109

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.214

Gnomad4 OTH exome

AF:

0.202

GnomAD4 genome

AF:

0.206

AC:

31311

AN:

152078

Hom.:

3296

Cov.:

AF XY:

0.202

AC XY:

15056

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.267

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.137

Gnomad4 FIN

AF:

0.165

Gnomad4 NFE

AF:

0.215

Gnomad4 OTH

AF:

0.208

Alfa

AF:

0.220

Hom.:

1006

Bravo

AF:

0.213

Asia WGS

AF:

0.118

AC:

413

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

1.6

DANN

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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