rs16986621

Positions:

• chr22-25999336-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.6288-3929A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0651 in 152,184 control chromosomes in the GnomAD database, including 708 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 0.065 (708 hom., cov: 31)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303

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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.6288-3929A>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.6288-3929A>G		intron_variant		1	NM_032608.7	ENSP00000334563	A2

Frequencies

GnomAD3 genomes AF: 0.0651 AC: 9904 AN: 152068 Hom.: 707 Cov.: 31

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.0917

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0456

Gnomad OTH AF: 0.0866

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

GnomAD4 genome AF: 0.0651 AC: 9908 AN: 152184 Hom.: 708 Cov.: 31 AF XY: 0.0718 AC XY: 5346 AN XY: 74406

Gnomad4 AFR AF: 0.0130

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.0917

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.0769

Gnomad4 FIN AF: 0.0953

Gnomad4 NFE AF: 0.0456

Gnomad4 OTH AF: 0.0853

Alfa AF: 0.0415 Hom.: 104

Bravo AF: 0.0717

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.9
DANN	Benign	0.89

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: rs16986621; hg19: chr22-26395302;