22-25761347-C-A

Position:

• chr22-25761347-C-A

Variant summary

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

The NM_032608.7(MYO18B):​c.39+216C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,980 control chromosomes in the GnomAD database, including 4,772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (4772 hom., cov: 32)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.212

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-25761347-C-A is Benign according to our data. Variant chr22-25761347-C-A is described in ClinVar as [Benign]. Clinvar id is 1245502.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO18B	NM_032608.7	c.39+216C>A		intron_variant		ENST00000335473.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO18B	ENST00000335473.12	c.39+216C>A		intron_variant		1	NM_032608.7	A2
MYO18B	ENST00000407587.6	c.39+216C>A		intron_variant		1		P5
MYO18B	ENST00000536101.5	c.39+216C>A		intron_variant		1		A2
MYO18B	ENST00000539302.5	c.39+216C>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36885 AN: 151862 Hom.: 4755 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.243 AC: 36927 AN: 151980 Hom.: 4772 Cov.: 32 AF XY: 0.238 AC XY: 17679 AN XY: 74264

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.243

Alfa AF: 0.0686 Hom.: 49

Bravo AF: 0.257

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

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs112270883; hg19: chr22-26157314;