22-25761350-G-C

Variant names:

• chr22-25761350-G-C
• rs5761166
• NM_032608.7:c.39+219G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032608.7(MYO18B):​c.39+219G>C 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 151,738 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: -0.841
• Publications: 3 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), Ambry Genetics, G2P, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 22-25761350-G-C is Benign according to our data. Variant chr22-25761350-G-C is described in ClinVar as Benign. ClinVar VariationId is 1287380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 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.39+219G>C		intron	N/A	NP_115997.5
	MYO18B	NM_001318245.2		c.39+219G>C		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.39+219G>C		intron	N/A	ENSP00000334563.8	Q8IUG5-1
	MYO18B	ENST00000407587.6	TSL:1	c.39+219G>C		intron	N/A	ENSP00000386096.2	Q8IUG5-3
	MYO18B	ENST00000536101.5	TSL:1	c.39+219G>C		intron	N/A	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36880 AN: 151620 Hom.: 4755 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.165

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: 36922 AN: 151738 Hom.: 4772 Cov.: 32 AF XY: 0.238 AC XY: 17674 AN XY: 74132

African (AFR) AF: 0.344 AC: 14180 AN: 41236

American (AMR) AF: 0.197 AC: 3015 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 984 AN: 3468

East Asian (EAS) AF: 0.168 AC: 861 AN: 5136

South Asian (SAS) AF: 0.144 AC: 695 AN: 4810

European-Finnish (FIN) AF: 0.165 AC: 1741 AN: 10564

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14692 AN: 67936

Other (OTH) AF: 0.244 AC: 514 AN: 2110

Alfa AF: 0.0611 Hom.: 49

Bravo AF: 0.257

Asia WGS AF: 0.154 AC: 539 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.41
DANN	Benign	0.41
PhyloP100		-0.84
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: rs5761166; hg19: chr22-26157317;