22-25912269-A-G

Variant names:

• chr22-25912269-A-G
• rs1476053
• NM_032608.7:c.5364+1219A>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.5364+1219A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 152,224 control chromosomes in the GnomAD database, including 62,334 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 0.90 (62334 hom., cov: 32)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 1 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, ClinGen, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.955 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	NM_032608.7	MANE Select	c.5364+1219A>G		intron	N/A	NP_115997.5
	MYO18B	NM_001318245.2		c.5367+1219A>G		intron	N/A	NP_001305174.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	ENST00000335473.12	TSL:1 MANE Select	c.5364+1219A>G		intron	N/A	ENSP00000334563.8
	MYO18B	ENST00000407587.6	TSL:1	c.5367+1219A>G		intron	N/A	ENSP00000386096.2
	MYO18B	ENST00000536101.5	TSL:1	c.5364+1219A>G		intron	N/A	ENSP00000441229.1

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137253 AN: 152106 Hom.: 62293 Cov.: 32

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.913

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

GnomAD4 genome AF: 0.902 AC: 137343 AN: 152224 Hom.: 62334 Cov.: 32 AF XY: 0.896 AC XY: 66641 AN XY: 74398

African (AFR) AF: 0.963 AC: 40018 AN: 41560

American (AMR) AF: 0.769 AC: 11756 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 3272 AN: 3470

East Asian (EAS) AF: 0.765 AC: 3938 AN: 5150

South Asian (SAS) AF: 0.814 AC: 3924 AN: 4820

European-Finnish (FIN) AF: 0.859 AC: 9095 AN: 10586

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.915 AC: 62237 AN: 68028

Other (OTH) AF: 0.905 AC: 1913 AN: 2114

Alfa AF: 0.910 Hom.: 7849

Bravo AF: 0.899

Asia WGS AF: 0.787 AC: 2739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.8
DANN	Benign	0.70
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1476053; hg19: chr22-26308236;