chr22-25743411-A-C

Variant names:

• chr22-25743411-A-C
• rs5761163
• NM_032608.7:c.-110+1118A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032608.7(MYO18B):​c.-110+1118A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	NM_032608.7	MANE Select	c.-110+1118A>C		intron	N/A	NP_115997.5
	MYO18B	NM_001318245.2		c.-110+1118A>C		intron	N/A	NP_001305174.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	ENST00000335473.12	TSL:1 MANE Select	c.-110+1118A>C		intron	N/A	ENSP00000334563.8
	MYO18B	ENST00000407587.6	TSL:1	c.-110+1118A>C		intron	N/A	ENSP00000386096.2
	MYO18B	ENST00000536101.5	TSL:1	c.-110+1118A>C		intron	N/A	ENSP00000441229.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 3102

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.90
DANN	Benign	0.45
PhyloP100		-0.36

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: rs5761163; hg19: chr22-26139378;