22-25877922-C-T

Variant names:

• chr22-25877922-C-T
• rs5752240
• NM_032608.7:c.4225-37C>T

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.4225-37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,525,914 control chromosomes in the GnomAD database, including 80,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9543 hom., cov: 33)
  • Exomes 𝑓: 0.32 (71141 hom.)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.951
• 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-AS1 (HGNC:40831): (MYO18B antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-25877922-C-T is Benign according to our data. Variant chr22-25877922-C-T is described in ClinVar as Benign. ClinVar VariationId is 1242816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 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.4225-37C>T		intron	N/A	NP_115997.5
	MYO18B	NM_001318245.2		c.4228-37C>T		intron	N/A	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.4225-37C>T		intron	N/A	ENSP00000334563.8	Q8IUG5-1
	MYO18B	ENST00000407587.6	TSL:1	c.4228-37C>T		intron	N/A	ENSP00000386096.2	Q8IUG5-3
	MYO18B	ENST00000536101.5	TSL:1	c.4225-37C>T		intron	N/A	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52343 AN: 151932 Hom.: 9525 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.333

GnomAD2 exomes AF: 0.318 AC: 51061 AN: 160470 AF XY: 0.322

Gnomad AFR exome AF: 0.452

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.257

Gnomad EAS exome AF: 0.514

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.315

GnomAD4 exome AF: 0.318 AC: 437102 AN: 1373862 Hom.: 71141 Cov.: 21 AF XY: 0.318 AC XY: 216040 AN XY: 679316

African (AFR) AF: 0.455 AC: 14183 AN: 31156

American (AMR) AF: 0.204 AC: 7270 AN: 35620

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 6431 AN: 24930

East Asian (EAS) AF: 0.479 AC: 17118 AN: 35704

South Asian (SAS) AF: 0.349 AC: 27385 AN: 78366

European-Finnish (FIN) AF: 0.332 AC: 16413 AN: 49422

Middle Eastern (MID) AF: 0.375 AC: 2121 AN: 5656

European-Non Finnish (NFE) AF: 0.310 AC: 326871 AN: 1055724

Other (OTH) AF: 0.337 AC: 19310 AN: 57284

GnomAD4 genome AF: 0.345 AC: 52400 AN: 152052 Hom.: 9543 Cov.: 33 AF XY: 0.345 AC XY: 25638 AN XY: 74312

African (AFR) AF: 0.436 AC: 18088 AN: 41446

American (AMR) AF: 0.236 AC: 3602 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 898 AN: 3464

East Asian (EAS) AF: 0.495 AC: 2562 AN: 5178

South Asian (SAS) AF: 0.353 AC: 1698 AN: 4804

European-Finnish (FIN) AF: 0.334 AC: 3528 AN: 10568

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20862 AN: 68000

Other (OTH) AF: 0.338 AC: 713 AN: 2112

Alfa AF: 0.312 Hom.: 3077

Bravo AF: 0.343

Asia WGS AF: 0.412 AC: 1432 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.67
PhyloP100		-0.95
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: rs5752240; hg19: chr22-26273889; COSMIC: COSV59135257;