rs5752205

Variant names:

• chr22-25781953-G-A
• rs5752205
• NM_032608.7:c.2312+119G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032608.7(MYO18B):​c.2312+119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00871 in 651,984 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (89 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (63 hom.)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.830
• Publications: 1 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 22-25781953-G-A is Benign according to our data. Variant chr22-25781953-G-A is described in ClinVar as Benign. ClinVar VariationId is 1183853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.063 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032608.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	NM_032608.7	MANE Select	c.2312+119G>A		intron	N/A	NP_115997.5
	MYO18B	NM_001318245.2		c.2312+119G>A		intron	N/A	NP_001305174.1	Q8IUG5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	ENST00000335473.12	TSL:1 MANE Select	c.2312+119G>A		intron	N/A	ENSP00000334563.8	Q8IUG5-1
	MYO18B	ENST00000407587.6	TSL:1	c.2312+119G>A		intron	N/A	ENSP00000386096.2	Q8IUG5-3
	MYO18B	ENST00000536101.5	TSL:1	c.2312+119G>A		intron	N/A	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3143 AN: 152200 Hom.: 89 Cov.: 33

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00838

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0384

Gnomad SAS AF: 0.0103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00505 AC: 2524 AN: 499666 Hom.: 63 AF XY: 0.00489 AC XY: 1234 AN XY: 252212

African (AFR) AF: 0.0698 AC: 852 AN: 12200

American (AMR) AF: 0.00621 AC: 65 AN: 10468

Ashkenazi Jewish (ASJ) AF: 0.000336 AC: 4 AN: 11892

East Asian (EAS) AF: 0.0336 AC: 855 AN: 25426

South Asian (SAS) AF: 0.0115 AC: 255 AN: 22106

European-Finnish (FIN) AF: 0.000152 AC: 4 AN: 26282

Middle Eastern (MID) AF: 0.00587 AC: 12 AN: 2044

European-Non Finnish (NFE) AF: 0.000580 AC: 211 AN: 363880

Other (OTH) AF: 0.0105 AC: 266 AN: 25368

GnomAD4 genome AF: 0.0207 AC: 3152 AN: 152318 Hom.: 89 Cov.: 33 AF XY: 0.0207 AC XY: 1540 AN XY: 74482

African (AFR) AF: 0.0651 AC: 2703 AN: 41546

American (AMR) AF: 0.00836 AC: 128 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.0385 AC: 200 AN: 5190

South Asian (SAS) AF: 0.0103 AC: 50 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68030

Other (OTH) AF: 0.0137 AC: 29 AN: 2114

Alfa AF: 0.0142 Hom.: 14

Bravo AF: 0.0235

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.3
DANN	Benign	0.77
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism

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: rs5752205; hg19: chr22-26177920;