22-25877867-A-C

Position:

• chr22-25877867-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000335473.12(MYO18B):​c.4225-92A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 919,100 control chromosomes in the GnomAD database, including 97,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14808 hom., cov: 33)
  • Exomes 𝑓: 0.46 (82496 hom.)
• Consequence: MYO18B ENST00000335473.12 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.724

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-25877867-A-C is Benign according to our data. Variant chr22-25877867-A-C is described in ClinVar as [Benign]. Clinvar id is 1271579.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.4225-92A>C		intron_variant		ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.4225-92A>C		intron_variant		1	NM_032608.7	ENSP00000334563	A2
MYO18B-AS1	ENST00000453457.7	n.1128-566T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65951 AN: 151786 Hom.: 14800 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: 0.396

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.459 AC: 352317 AN: 767196 Hom.: 82496 AF XY: 0.458 AC XY: 180926 AN XY: 395392

Gnomad4 AFR exome AF: 0.315

Gnomad4 AMR exome AF: 0.646

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.476

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.431

GnomAD4 genome AF: 0.434 AC: 65977 AN: 151904 Hom.: 14808 Cov.: 33 AF XY: 0.437 AC XY: 32465 AN XY: 74252

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.415

Alfa AF: 0.452 Hom.: 1980

Bravo AF: 0.436

Asia WGS AF: 0.441 AC: 1533 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs4822666; hg19: chr22-26273834;