22-25762943-C-G

Variant names:

• chr22-25762943-C-G
• rs2331158
• NM_032608.7:c.40-288C>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.40-288C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 576,634 control chromosomes in the GnomAD database, including 29,282 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (8129 hom., cov: 33)
  • Exomes 𝑓: 0.29 (21153 hom.)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.497
• 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=-0.82).
• BP6: Variant 22-25762943-C-G is Benign according to our data. Variant chr22-25762943-C-G is described in ClinVar as [Benign]. Clinvar id is 1281393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.40-288C>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.40-288C>G		intron_variant	Intron 2 of 43	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.40-288C>G		intron_variant	Intron 2 of 43	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.40-288C>G		intron_variant	Intron 2 of 42	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.40-288C>G		intron_variant	Intron 1 of 41	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46226 AN: 152036 Hom.: 8105 Cov.: 33

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.286 AC: 121567 AN: 424480 Hom.: 21153 AF XY: 0.286 AC XY: 67309 AN XY: 235636

African (AFR) AF: 0.397 AC: 5075 AN: 12784

American (AMR) AF: 0.485 AC: 18101 AN: 37350

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 3248 AN: 13956

East Asian (EAS) AF: 0.655 AC: 12111 AN: 18478

South Asian (SAS) AF: 0.374 AC: 24298 AN: 64884

European-Finnish (FIN) AF: 0.257 AC: 6797 AN: 26400

Middle Eastern (MID) AF: 0.219 AC: 685 AN: 3134

European-Non Finnish (NFE) AF: 0.201 AC: 45576 AN: 226708

Other (OTH) AF: 0.273 AC: 5676 AN: 20786

GnomAD4 genome AF: 0.304 AC: 46287 AN: 152154 Hom.: 8129 Cov.: 33 AF XY: 0.312 AC XY: 23208 AN XY: 74380

African (AFR) AF: 0.396 AC: 16452 AN: 41498

American (AMR) AF: 0.382 AC: 5834 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 808 AN: 3468

East Asian (EAS) AF: 0.645 AC: 3340 AN: 5176

South Asian (SAS) AF: 0.395 AC: 1906 AN: 4820

European-Finnish (FIN) AF: 0.273 AC: 2891 AN: 10598

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14304 AN: 68000

Other (OTH) AF: 0.284 AC: 599 AN: 2112

Alfa AF: 0.144 Hom.: 263

Bravo AF: 0.315

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.65
PhyloP100		0.50
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: rs2331158; hg19: chr22-26158910; COSMIC: COSV59135233;