rs3859865

Variant names:

• chr22-25762317-G-A
• rs3859865
• NM_032608.7:c.40-914G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032608.7(MYO18B):​c.40-914G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,176 control chromosomes in the GnomAD database, including 3,349 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 0.21 (3349 hom., cov: 33)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.40-914G>A		intron_variant	Intron 2 of 43	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.40-914G>A		intron_variant	Intron 2 of 43	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.40-914G>A		intron_variant	Intron 2 of 43	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.40-914G>A		intron_variant	Intron 2 of 42	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.40-914G>A		intron_variant	Intron 1 of 41	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31496 AN: 152056 Hom.: 3338 Cov.: 33

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.207 AC: 31526 AN: 152176 Hom.: 3349 Cov.: 33 AF XY: 0.204 AC XY: 15166 AN XY: 74414

African (AFR) AF: 0.230 AC: 9554 AN: 41516

American (AMR) AF: 0.183 AC: 2804 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 925 AN: 3466

East Asian (EAS) AF: 0.122 AC: 631 AN: 5172

South Asian (SAS) AF: 0.137 AC: 660 AN: 4822

European-Finnish (FIN) AF: 0.164 AC: 1740 AN: 10594

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14553 AN: 67988

Other (OTH) AF: 0.206 AC: 436 AN: 2112

Alfa AF: 0.213 Hom.: 2677

Bravo AF: 0.215

Asia WGS AF: 0.122 AC: 428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.32
DANN	Benign	0.50
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3859865; hg19: chr22-26158284;