22-25761347-C-G

Variant names:

• chr22-25761347-C-G
• rs112270883
• NM_032608.7:c.39+216C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_032608.7(MYO18B):​c.39+216C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00404 in 152,038 control chromosomes in the GnomAD database, including 3 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 0.0040 (3 hom., cov: 32)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 2 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=-0.91).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00404 (614/152038) while in subpopulation SAS AF = 0.00956 (46/4814). AF 95% confidence interval is 0.00832. There are 3 homozygotes in GnomAd4. There are 328 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.39+216C>G		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.39+216C>G		intron_variant	Intron 2 of 43	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.39+216C>G		intron_variant	Intron 2 of 43	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.39+216C>G		intron_variant	Intron 2 of 42	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.39+216C>G		intron_variant	Intron 1 of 41	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes AF: 0.00405 AC: 615 AN: 151920 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00910

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00774

Gnomad SAS AF: 0.00955

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.00574

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

GnomAD4 genome AF: 0.00404 AC: 614 AN: 152038 Hom.: 3 Cov.: 32 AF XY: 0.00441 AC XY: 328 AN XY: 74306

African (AFR) AF: 0.00908 AC: 376 AN: 41428

American (AMR) AF: 0.00562 AC: 86 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00775 AC: 40 AN: 5158

South Asian (SAS) AF: 0.00956 AC: 46 AN: 4814

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10608

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.000648 AC: 44 AN: 67952

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.000364 Hom.: 49

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.96
DANN	Benign	0.47
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs112270883; hg19: chr22-26157314;