NM_032608.7:c.39+46A>G

Variant names:

• chr22-25761177-A-G
• rs17623980
• NM_032608.7:c.39+46A>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.39+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,606,262 control chromosomes in the GnomAD database, including 34,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3296 hom., cov: 33)
  • Exomes 𝑓: 0.21 (31510 hom.)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.114
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-25761177-A-G is Benign according to our data. Variant chr22-25761177-A-G is described in ClinVar as [Benign]. Clinvar id is 1279814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.39+46A>G		intron_variant	Intron 2 of 43	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.39+46A>G		intron_variant	Intron 2 of 43	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.39+46A>G		intron_variant	Intron 2 of 43	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.39+46A>G		intron_variant	Intron 2 of 42	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.39+46A>G		intron_variant	Intron 1 of 41	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31282 AN: 151960 Hom.: 3285 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.211

GnomAD2 exomes AF: 0.194 AC: 47490 AN: 245252 AF XY: 0.192

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.199

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.121

Gnomad FIN exome AF: 0.164

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.206 AC: 298989 AN: 1454184 Hom.: 31510 Cov.: 30 AF XY: 0.204 AC XY: 147541 AN XY: 723792

African (AFR) AF: 0.233 AC: 7792 AN: 33432

American (AMR) AF: 0.198 AC: 8861 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 6783 AN: 26080

East Asian (EAS) AF: 0.109 AC: 4329 AN: 39684

South Asian (SAS) AF: 0.138 AC: 11907 AN: 86162

European-Finnish (FIN) AF: 0.162 AC: 8024 AN: 49628

Middle Eastern (MID) AF: 0.271 AC: 1557 AN: 5756

European-Non Finnish (NFE) AF: 0.214 AC: 237590 AN: 1108572

Other (OTH) AF: 0.202 AC: 12146 AN: 60182

GnomAD4 genome AF: 0.206 AC: 31311 AN: 152078 Hom.: 3296 Cov.: 33 AF XY: 0.202 AC XY: 15056 AN XY: 74358

African (AFR) AF: 0.226 AC: 9375 AN: 41476

American (AMR) AF: 0.179 AC: 2730 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 925 AN: 3466

East Asian (EAS) AF: 0.119 AC: 614 AN: 5170

South Asian (SAS) AF: 0.137 AC: 659 AN: 4822

European-Finnish (FIN) AF: 0.165 AC: 1751 AN: 10586

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14595 AN: 67964

Other (OTH) AF: 0.208 AC: 439 AN: 2108

Alfa AF: 0.220 Hom.: 1020

Bravo AF: 0.213

Asia WGS AF: 0.118 AC: 413 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.36
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17623980; hg19: chr22-26157144; COSMIC: COSV59147738; COSMIC: COSV59147738;