22-25877687-C-T

Position:

• chr22-25877687-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000335473.12(MYO18B):​c.4225-272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,794 control chromosomes in the GnomAD database, including 14,297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (14297 hom., cov: 31)
• Consequence: MYO18B ENST00000335473.12 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.305

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 22-25877687-C-T is Benign according to our data. Variant chr22-25877687-C-T is described in ClinVar as [Benign]. Clinvar id is 1271075.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.4225-272C>T		intron_variant		ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.4225-272C>T		intron_variant		1	NM_032608.7	ENSP00000334563	A2
MYO18B-AS1	ENST00000453457.7	n.1128-386G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64344 AN: 151676 Hom.: 14291 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.424 AC: 64365 AN: 151794 Hom.: 14297 Cov.: 31 AF XY: 0.428 AC XY: 31740 AN XY: 74208

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.409

Alfa AF: 0.445 Hom.: 1887

Bravo AF: 0.424

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.94
CADD	Benign	5.7
DANN	Benign	0.58

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: rs9613031; hg19: chr22-26273654;