chr22-25778430-T-C

Variant names:

• chr22-25778430-T-C
• rs9613019
• NM_032608.7:c.2068+649T>C

Variant summary

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

The NM_032608.7(MYO18B):​c.2068+649T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,782 control chromosomes in the GnomAD database, including 21,272 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 0.51 (21272 hom., cov: 30)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.2068+649T>C		intron_variant	Intron 8 of 43	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.2068+649T>C		intron_variant	Intron 8 of 43	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.2068+649T>C		intron_variant	Intron 8 of 43	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.2068+649T>C		intron_variant	Intron 8 of 42	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.2068+649T>C		intron_variant	Intron 7 of 41	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 77940 AN: 151664 Hom.: 21269 Cov.: 30

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.514 AC: 77947 AN: 151782 Hom.: 21272 Cov.: 30 AF XY: 0.513 AC XY: 38051 AN XY: 74154

African (AFR) AF: 0.309 AC: 12785 AN: 41330

American (AMR) AF: 0.597 AC: 9106 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1573 AN: 3468

East Asian (EAS) AF: 0.633 AC: 3268 AN: 5166

South Asian (SAS) AF: 0.557 AC: 2671 AN: 4794

European-Finnish (FIN) AF: 0.550 AC: 5792 AN: 10530

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40894 AN: 67934

Other (OTH) AF: 0.536 AC: 1127 AN: 2104

Alfa AF: 0.565 Hom.: 9068

Bravo AF: 0.504

Asia WGS AF: 0.585 AC: 2031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.37
PhyloP100		-1.7
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: rs9613019; hg19: chr22-26174397;