rs9613019

Positions:

• chr22-25778430-T-C

Variant summary

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

The NM_032608.7(MYO18B):​c.2068+649T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,782 control chromosomes in the GnomAD database, including 21,272 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 0.51 (21272 hom., cov: 30)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO18B	NM_032608.7	c.2068+649T>C		intron_variant		ENST00000335473.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO18B	ENST00000335473.12	c.2068+649T>C		intron_variant		1	NM_032608.7	A2

Frequencies

GnomAD3 genomes AF: 0.514 AC: 77940 AN: 151664 Hom.: 21269 Cov.: 30

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.514 AC: 77947 AN: 151782 Hom.: 21272 Cov.: 30 AF XY: 0.513 AC XY: 38051 AN XY: 74154

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.536

Alfa AF: 0.566 Hom.: 5448

Bravo AF: 0.504

Asia WGS AF: 0.585 AC: 2031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.37

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: rs9613019; hg19: chr22-26174397;