chr22-25746525-A-C

Variant names:

• chr22-25746525-A-C
• rs133856
• NM_032608.7:c.-110+4232A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032608.7(MYO18B):​c.-110+4232A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,950 control chromosomes in the GnomAD database, including 17,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.43 (17102 hom., cov: 32)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.747
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 22-25746525-A-C is Benign according to our data. Variant chr22-25746525-A-C is described in ClinVar as [Benign]. Clinvar id is 1598718.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.-110+4232A>C		intron_variant	Intron 1 of 43	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.-110+4232A>C		intron_variant	Intron 1 of 43	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.-110+4232A>C		intron_variant	Intron 1 of 43	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.-110+4232A>C		intron_variant	Intron 1 of 42	1		ENSP00000441229.1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64853 AN: 151834 Hom.: 17054 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.427 AC: 64947 AN: 151950 Hom.: 17102 Cov.: 32 AF XY: 0.428 AC XY: 31791 AN XY: 74238

African (AFR) AF: 0.749 AC: 31045 AN: 41432

American (AMR) AF: 0.318 AC: 4853 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 949 AN: 3470

East Asian (EAS) AF: 0.301 AC: 1553 AN: 5154

South Asian (SAS) AF: 0.490 AC: 2355 AN: 4804

European-Finnish (FIN) AF: 0.361 AC: 3792 AN: 10516

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19247 AN: 67982

Other (OTH) AF: 0.370 AC: 780 AN: 2110

Alfa AF: 0.258 Hom.: 775

Bravo AF: 0.437

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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	-0.93
CADD	Benign	0.75
DANN	Benign	0.54
PhyloP100		-0.75
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: rs133856; hg19: chr22-26142492;