22-25877869-G-T

Variant names:

• chr22-25877869-G-T
• rs4822667
• NM_032608.7:c.4225-90G>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.4225-90G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 972,664 control chromosomes in the GnomAD database, including 104,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14807 hom., cov: 33)
  • Exomes 𝑓: 0.46 (89341 hom.)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.21
• Publications: 3 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=-1.03).
• BP6: Variant 22-25877869-G-T is Benign according to our data. Variant chr22-25877869-G-T is described in ClinVar as Benign. ClinVar VariationId is 1232139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.559 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.4225-90G>T		intron	N/A	NP_115997.5
	MYO18B	NM_001318245.2		c.4228-90G>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.4225-90G>T		intron	N/A	ENSP00000334563.8	Q8IUG5-1
	MYO18B	ENST00000407587.6	TSL:1	c.4228-90G>T		intron	N/A	ENSP00000386096.2	Q8IUG5-3
	MYO18B	ENST00000536101.5	TSL:1	c.4225-90G>T		intron	N/A	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65949 AN: 151732 Hom.: 14799 Cov.: 33

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.463 AC: 379777 AN: 820812 Hom.: 89341 AF XY: 0.461 AC XY: 193838 AN XY: 420646

African (AFR) AF: 0.317 AC: 6285 AN: 19824

American (AMR) AF: 0.646 AC: 18497 AN: 28644

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 7281 AN: 19020

East Asian (EAS) AF: 0.477 AC: 15249 AN: 31998

South Asian (SAS) AF: 0.414 AC: 24463 AN: 59058

European-Finnish (FIN) AF: 0.490 AC: 22969 AN: 46894

Middle Eastern (MID) AF: 0.373 AC: 1650 AN: 4418

European-Non Finnish (NFE) AF: 0.466 AC: 266799 AN: 572710

Other (OTH) AF: 0.434 AC: 16584 AN: 38246

GnomAD4 genome AF: 0.434 AC: 65975 AN: 151852 Hom.: 14807 Cov.: 33 AF XY: 0.437 AC XY: 32461 AN XY: 74218

African (AFR) AF: 0.328 AC: 13581 AN: 41398

American (AMR) AF: 0.569 AC: 8693 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1360 AN: 3468

East Asian (EAS) AF: 0.437 AC: 2261 AN: 5178

South Asian (SAS) AF: 0.416 AC: 1996 AN: 4802

European-Finnish (FIN) AF: 0.499 AC: 5250 AN: 10516

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31498 AN: 67900

Other (OTH) AF: 0.415 AC: 878 AN: 2116

Alfa AF: 0.382 Hom.: 1734

Bravo AF: 0.447

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	-1.0
CADD	Benign	0.36
DANN	Benign	0.46
PhyloP100		-1.2
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: rs4822667; hg19: chr22-26273836;