rs8139900

Variant names:

• chr22-25998758-A-G
• rs8139900
• NM_032608.7:c.6288-4507A>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.6288-4507A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,878 control chromosomes in the GnomAD database, including 23,196 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 0.52 (23196 hom., cov: 32)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.6288-4507A>G		intron_variant	Intron 40 of 43	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.6288-4507A>G		intron_variant	Intron 40 of 43	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.6291-4507A>G		intron_variant	Intron 40 of 43	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.6288-4507A>G		intron_variant	Intron 40 of 42	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.*3746-4507A>G		intron_variant	Intron 38 of 41	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79023 AN: 151760 Hom.: 23167 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.521 AC: 79099 AN: 151878 Hom.: 23196 Cov.: 32 AF XY: 0.507 AC XY: 37635 AN XY: 74232

African (AFR) AF: 0.784 AC: 32448 AN: 41412

American (AMR) AF: 0.385 AC: 5876 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1585 AN: 3470

East Asian (EAS) AF: 0.149 AC: 771 AN: 5170

South Asian (SAS) AF: 0.332 AC: 1594 AN: 4804

European-Finnish (FIN) AF: 0.308 AC: 3261 AN: 10576

Middle Eastern (MID) AF: 0.521 AC: 151 AN: 290

European-Non Finnish (NFE) AF: 0.471 AC: 31953 AN: 67876

Other (OTH) AF: 0.488 AC: 1030 AN: 2110

Alfa AF: 0.485 Hom.: 78414

Bravo AF: 0.541

Asia WGS AF: 0.253 AC: 884 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	0.039
DANN	Benign	0.67
PhyloP100		-0.96
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: rs8139900; hg19: chr22-26394724; COSMIC: COSV59136077;