22-25882501-C-T

Position:

• chr22-25882501-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032608.7(MYO18B):​c.4314+4453C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,086 control chromosomes in the GnomAD database, including 26,856 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (26856 hom., cov: 32)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.4314+4453C>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.4314+4453C>T		intron_variant		1	NM_032608.7	ENSP00000334563	A2
MYO18B-AS1	ENST00000453457.7	n.1127+2215G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89161 AN: 151968 Hom.: 26829 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.587 AC: 89234 AN: 152086 Hom.: 26856 Cov.: 32 AF XY: 0.592 AC XY: 44011 AN XY: 74334

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.542

Alfa AF: 0.530 Hom.: 22575

Bravo AF: 0.593

Asia WGS AF: 0.766 AC: 2661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.22

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: rs695670; hg19: chr22-26278468;