22-25882501-C-T

Variant names:

• chr22-25882501-C-T
• rs695670
• NM_032608.7:c.4314+4453C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032608.7(MYO18B):​c.4314+4453C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,086 control chromosomes in the GnomAD database, including 26,856 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (26856 hom., cov: 32)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 9 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-AS1 (HGNC:40831): (MYO18B antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	NM_032608.7	MANE Select	c.4314+4453C>T		intron	N/A	NP_115997.5
	MYO18B	NM_001318245.2		c.4317+4453C>T		intron	N/A	NP_001305174.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	ENST00000335473.12	TSL:1 MANE Select	c.4314+4453C>T		intron	N/A	ENSP00000334563.8
	MYO18B	ENST00000407587.6	TSL:1	c.4317+4453C>T		intron	N/A	ENSP00000386096.2
	MYO18B	ENST00000536101.5	TSL:1	c.4314+4453C>T		intron	N/A	ENSP00000441229.1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89161 AN: 151968 Hom.: 26829 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.587 AC: 89234 AN: 152086 Hom.: 26856 Cov.: 32 AF XY: 0.592 AC XY: 44011 AN XY: 74334

African (AFR) AF: 0.662 AC: 27475 AN: 41482

American (AMR) AF: 0.644 AC: 9841 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1238 AN: 3468

East Asian (EAS) AF: 0.846 AC: 4386 AN: 5186

South Asian (SAS) AF: 0.700 AC: 3378 AN: 4826

European-Finnish (FIN) AF: 0.544 AC: 5739 AN: 10556

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35354 AN: 67972

Other (OTH) AF: 0.542 AC: 1145 AN: 2112

Alfa AF: 0.541 Hom.: 34041

Bravo AF: 0.593

Asia WGS AF: 0.766 AC: 2661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.22
PhyloP100		-2.0
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: rs695670; hg19: chr22-26278468;