rs16986621

Variant names:

• chr22-25999336-A-G
• rs16986621
• NM_032608.7:c.6288-3929A>G

Variant summary

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

The ENST00000407587.6(MYO18B):​c.6291-3929A>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 ENST00000407587.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• 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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000407587.6. 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.6288-3929A>G		intron	N/A	NP_115997.5
	MYO18B	NM_001318245.2		c.6291-3929A>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.6288-3929A>G		intron	N/A	ENSP00000334563.8
	MYO18B	ENST00000407587.6	TSL:1	c.6291-3929A>G		intron	N/A	ENSP00000386096.2
	MYO18B	ENST00000536101.5	TSL:1	c.6288-3929A>G		intron	N/A	ENSP00000441229.1

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

African (AFR) AF: 0.0130 AC: 538 AN: 41526

American (AMR) AF: 0.195 AC: 2974 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0917 AC: 318 AN: 3468

East Asian (EAS) AF: 0.266 AC: 1374 AN: 5168

South Asian (SAS) AF: 0.0769 AC: 370 AN: 4810

European-Finnish (FIN) AF: 0.0953 AC: 1011 AN: 10606

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0456 AC: 3101 AN: 68012

Other (OTH) AF: 0.0853 AC: 180 AN: 2110

Alfa AF: 0.0424 Hom.: 115

Bravo AF: 0.0717

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.9
DANN	Benign	0.89
PhyloP100		0.30
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: rs16986621; hg19: chr22-26395302;