22-25743411-A-G

Variant names:

• chr22-25743411-A-G
• rs5761163
• NM_032608.7:c.-110+1118A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032608.7(MYO18B):​c.-110+1118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,082 control chromosomes in the GnomAD database, including 3,719 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3719 hom., cov: 31)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• Publications: 9 publications found

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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032608.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	NM_032608.7	MANE Select	c.-110+1118A>G		intron	N/A	NP_115997.5
	MYO18B	NM_001318245.2		c.-110+1118A>G		intron	N/A	NP_001305174.1	Q8IUG5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	ENST00000335473.12	TSL:1 MANE Select	c.-110+1118A>G		intron	N/A	ENSP00000334563.8	Q8IUG5-1
	MYO18B	ENST00000407587.6	TSL:1	c.-110+1118A>G		intron	N/A	ENSP00000386096.2	Q8IUG5-3
	MYO18B	ENST00000536101.5	TSL:1	c.-110+1118A>G		intron	N/A	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30342 AN: 151960 Hom.: 3709 Cov.: 31

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.200 AC: 30356 AN: 152082 Hom.: 3719 Cov.: 31 AF XY: 0.199 AC XY: 14810 AN XY: 74332

African (AFR) AF: 0.0660 AC: 2740 AN: 41524

American (AMR) AF: 0.276 AC: 4216 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1089 AN: 3468

East Asian (EAS) AF: 0.376 AC: 1937 AN: 5148

South Asian (SAS) AF: 0.156 AC: 749 AN: 4802

European-Finnish (FIN) AF: 0.163 AC: 1725 AN: 10582

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17238 AN: 67962

Other (OTH) AF: 0.214 AC: 451 AN: 2110

Alfa AF: 0.218 Hom.: 3102

Bravo AF: 0.205

Asia WGS AF: 0.239 AC: 830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.42
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5761163; hg19: chr22-26139378;