22-25877822-T-C

Position:

• chr22-25877822-T-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.4225-137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 629,792 control chromosomes in the GnomAD database, including 36,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9582 hom., cov: 32)
  • Exomes 𝑓: 0.33 (26510 hom.)
• Consequence: MYO18B ENST00000335473.12 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.60

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=-1.04).
• BP6: Variant 22-25877822-T-C is Benign according to our data. Variant chr22-25877822-T-C is described in ClinVar as [Benign]. Clinvar id is 1239538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.4225-137T>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.4225-137T>C		intron_variant		1	NM_032608.7	ENSP00000334563	A2
MYO18B-AS1	ENST00000453457.7	n.1128-521A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52459 AN: 151964 Hom.: 9564 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.326 AC: 155909 AN: 477708 Hom.: 26510 AF XY: 0.327 AC XY: 81813 AN XY: 250356

Gnomad4 AFR exome AF: 0.446

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.359

Gnomad4 FIN exome AF: 0.335

Gnomad4 NFE exome AF: 0.309

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.345 AC: 52517 AN: 152084 Hom.: 9582 Cov.: 32 AF XY: 0.346 AC XY: 25706 AN XY: 74342

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.339

Alfa AF: 0.317 Hom.: 1549

Bravo AF: 0.343

Asia WGS AF: 0.423 AC: 1469 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	-1.0
CADD	Benign	0.74
DANN	Benign	0.31

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: rs5761293; hg19: chr22-26273789; COSMIC: COSV59133582;