chr22-25743411-A-G

Position:

• chr22-25743411-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.-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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.-110+1118A>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.-110+1118A>G		intron_variant		1	NM_032608.7	ENSP00000334563	A2
MYO18B	ENST00000407587.6	c.-110+1118A>G		intron_variant		1		ENSP00000386096	P5
MYO18B	ENST00000536101.5	c.-110+1118A>G		intron_variant		1		ENSP00000441229	A2

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

Gnomad4 AFR AF: 0.0660

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.214

Alfa AF: 0.212 Hom.: 2309

Bravo AF: 0.205

Asia WGS AF: 0.239 AC: 830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs5761163; hg19: chr22-26139378;