22-25781953-G-A

Position:

• chr22-25781953-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032608.7(MYO18B):​c.2312+119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00871 in 651,984 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (89 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (63 hom.)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.830

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 22-25781953-G-A is Benign according to our data. Variant chr22-25781953-G-A is described in ClinVar as [Benign]. Clinvar id is 1183853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.063 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.2312+119G>A		intron_variant		ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.2312+119G>A		intron_variant		1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.2312+119G>A		intron_variant		1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.2312+119G>A		intron_variant		1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.2312+119G>A		intron_variant		1		ENSP00000437587.1

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3143 AN: 152200 Hom.: 89 Cov.: 33

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00838

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0384

Gnomad SAS AF: 0.0103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00505 AC: 2524 AN: 499666 Hom.: 63 AF XY: 0.00489 AC XY: 1234 AN XY: 252212

Gnomad4 AFR exome AF: 0.0698

Gnomad4 AMR exome AF: 0.00621

Gnomad4 ASJ exome AF: 0.000336

Gnomad4 EAS exome AF: 0.0336

Gnomad4 SAS exome AF: 0.0115

Gnomad4 FIN exome AF: 0.000152

Gnomad4 NFE exome AF: 0.000580

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.0207 AC: 3152 AN: 152318 Hom.: 89 Cov.: 33 AF XY: 0.0207 AC XY: 1540 AN XY: 74482

Gnomad4 AFR AF: 0.0651

Gnomad4 AMR AF: 0.00836

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0385

Gnomad4 SAS AF: 0.0103

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0139 Hom.: 7

Bravo AF: 0.0235

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.3
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs5752205; hg19: chr22-26177920;