chr22-25912269-A-G

Position:

• chr22-25912269-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.5364+1219A>G		intron_variant		ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.5364+1219A>G		intron_variant		1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.5367+1219A>G		intron_variant		1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.5364+1219A>G		intron_variant		1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.*2822+1219A>G		intron_variant		1		ENSP00000437587.1

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

Gnomad4 AFR AF: 0.963

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.943

Gnomad4 EAS AF: 0.765

Gnomad4 SAS AF: 0.814

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.915

Gnomad4 OTH AF: 0.905

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.8
DANN	Benign	0.70

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: rs1476053; hg19: chr22-26308236;