rs9624909

Variant names:

• chr22-25826487-C-T
• rs9624909
• NM_032608.7:c.2774C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032608.7(MYO18B):​c.2774C>T​(p.Ser925Leu) variant causes a missense change. The variant allele was found at a frequency of 0.212 in 1,612,254 control chromosomes in the GnomAD database, including 38,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3373 hom., cov: 32)
  • Exomes 𝑓: 0.21 (35295 hom.)
• Consequence: MYO18B NM_032608.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.62
• Publications: 15 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018035173).
• BP6: Variant 22-25826487-C-T is Benign according to our data. Variant chr22-25826487-C-T is described in ClinVar as Benign. ClinVar VariationId is 1273583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032608.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	NM_032608.7	MANE Select	c.2774C>T	p.Ser925Leu	missense	Exon 14 of 44	NP_115997.5
	MYO18B	NM_001318245.2		c.2774C>T	p.Ser925Leu	missense	Exon 14 of 44	NP_001305174.1	Q8IUG5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	ENST00000335473.12	TSL:1 MANE Select	c.2774C>T	p.Ser925Leu	missense	Exon 14 of 44	ENSP00000334563.8	Q8IUG5-1
	MYO18B	ENST00000407587.6	TSL:1	c.2774C>T	p.Ser925Leu	missense	Exon 14 of 44	ENSP00000386096.2	Q8IUG5-3
	MYO18B	ENST00000536101.5	TSL:1	c.2774C>T	p.Ser925Leu	missense	Exon 14 of 43	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31280 AN: 152034 Hom.: 3367 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.210

GnomAD2 exomes AF: 0.184 AC: 45794 AN: 248730 AF XY: 0.184

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.198

Gnomad EAS exome AF: 0.00267

Gnomad FIN exome AF: 0.276

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.216

GnomAD4 exome AF: 0.213 AC: 310438 AN: 1460100 Hom.: 35295 Cov.: 31 AF XY: 0.210 AC XY: 152738 AN XY: 726354

African (AFR) AF: 0.198 AC: 6630 AN: 33454

American (AMR) AF: 0.128 AC: 5714 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 5133 AN: 26084

East Asian (EAS) AF: 0.00128 AC: 51 AN: 39690

South Asian (SAS) AF: 0.125 AC: 10747 AN: 86136

European-Finnish (FIN) AF: 0.275 AC: 14647 AN: 53340

Middle Eastern (MID) AF: 0.215 AC: 1236 AN: 5760

European-Non Finnish (NFE) AF: 0.229 AC: 254303 AN: 1110690

Other (OTH) AF: 0.199 AC: 11977 AN: 60314

GnomAD4 genome AF: 0.206 AC: 31300 AN: 152154 Hom.: 3373 Cov.: 32 AF XY: 0.206 AC XY: 15289 AN XY: 74376

African (AFR) AF: 0.199 AC: 8259 AN: 41506

American (AMR) AF: 0.184 AC: 2806 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 678 AN: 3470

East Asian (EAS) AF: 0.00271 AC: 14 AN: 5174

South Asian (SAS) AF: 0.105 AC: 509 AN: 4828

European-Finnish (FIN) AF: 0.281 AC: 2975 AN: 10576

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15265 AN: 67996

Other (OTH) AF: 0.207 AC: 437 AN: 2116

Alfa AF: 0.214 Hom.: 17452

Bravo AF: 0.202

TwinsUK AF: 0.248 AC: 920

ALSPAC AF: 0.221 AC: 852

ESP6500AA AF: 0.189 AC: 741

ESP6500EA AF: 0.217 AC: 1803

ExAC AF: 0.185 AC: 22314

Asia WGS AF: 0.0610 AC: 212 AN: 3478

EpiCase AF: 0.231

EpiControl AF: 0.228

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.3	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.6
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.98	D
Vest4		0.24
MPC		0.36
ClinPred		0.032	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.47
Mutation Taster		=92/8	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: rs9624909; hg19: chr22-26222454; COSMIC: COSV59136972;