rs61734946

Variant names:

• chr22-25761101-C-G
• rs61734946
• NM_032608.7:c.9C>G

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.9C>G​(p.Ile3Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,612,852 control chromosomes in the GnomAD database, including 26,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1737 hom., cov: 33)
  • Exomes 𝑓: 0.18 (24495 hom.)
• Consequence: MYO18B NM_032608.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.175
• Publications: 14 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), Ambry Genetics, G2P, Orphanet, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016304553).
• BP6: Variant 22-25761101-C-G is Benign according to our data. Variant chr22-25761101-C-G is described in ClinVar as Benign. ClinVar VariationId is 1321829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 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.9C>G	p.Ile3Met	missense	Exon 2 of 44	NP_115997.5
	MYO18B	NM_001318245.2		c.9C>G	p.Ile3Met	missense	Exon 2 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.9C>G	p.Ile3Met	missense	Exon 2 of 44	ENSP00000334563.8	Q8IUG5-1
	MYO18B	ENST00000407587.6	TSL:1	c.9C>G	p.Ile3Met	missense	Exon 2 of 44	ENSP00000386096.2	Q8IUG5-3
	MYO18B	ENST00000536101.5	TSL:1	c.9C>G	p.Ile3Met	missense	Exon 2 of 43	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20030 AN: 152148 Hom.: 1737 Cov.: 33

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.148

GnomAD2 exomes AF: 0.142 AC: 35447 AN: 248832 AF XY: 0.147

Gnomad AFR exome AF: 0.0352

Gnomad AMR exome AF: 0.0891

Gnomad ASJ exome AF: 0.243

Gnomad EAS exome AF: 0.000667

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.172

GnomAD4 exome AF: 0.176 AC: 256892 AN: 1460586 Hom.: 24495 Cov.: 32 AF XY: 0.175 AC XY: 127181 AN XY: 726634

African (AFR) AF: 0.0343 AC: 1149 AN: 33478

American (AMR) AF: 0.0928 AC: 4150 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 6488 AN: 26126

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39700

South Asian (SAS) AF: 0.110 AC: 9513 AN: 86222

European-Finnish (FIN) AF: 0.145 AC: 7649 AN: 52898

Middle Eastern (MID) AF: 0.213 AC: 1228 AN: 5768

European-Non Finnish (NFE) AF: 0.195 AC: 216869 AN: 1111342

Other (OTH) AF: 0.163 AC: 9826 AN: 60348

GnomAD4 genome AF: 0.132 AC: 20025 AN: 152266 Hom.: 1737 Cov.: 33 AF XY: 0.129 AC XY: 9588 AN XY: 74444

African (AFR) AF: 0.0393 AC: 1636 AN: 41578

American (AMR) AF: 0.112 AC: 1715 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.105 AC: 508 AN: 4826

European-Finnish (FIN) AF: 0.146 AC: 1551 AN: 10596

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13232 AN: 68002

Other (OTH) AF: 0.146 AC: 309 AN: 2114

Alfa AF: 0.184 Hom.: 2096

Bravo AF: 0.126

TwinsUK AF: 0.192 AC: 713

ALSPAC AF: 0.178 AC: 687

ESP6500AA AF: 0.0403 AC: 177

ESP6500EA AF: 0.189 AC: 1622

ExAC AF: 0.141 AC: 17150

Asia WGS AF: 0.0430 AC: 152 AN: 3478

EpiCase AF: 0.202

EpiControl AF: 0.204

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T
Eigen	Benign	0.077
Eigen_PC	Benign	-0.012
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.17
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Vest4		0.28
MPC		0.14
ClinPred		0.063	T
GERP RS		-0.90
Varity_R		0.21
gMVP		0.14
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61734946; hg19: chr22-26157068;