rs2227235

chr22-25930346-T-Cchr22-25930346-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032608.7(MYO18B):c.5517+8937T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,624 control chromosomes in the GnomAD database, including 2,534 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 0.15 (2534 hom., cov: 30)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO18B	NM_032608.7	c.5517+8937T>C		intron_variant		ENST00000335473.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO18B	ENST00000335473.12	c.5517+8937T>C		intron_variant		1	NM_032608.7	A2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22435 AN: 151506 Hom.: 2521 Cov.: 30

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.0479

Gnomad SAS AF: 0.0899

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.148 AC: 22486 AN: 151624 Hom.: 2534 Cov.: 30 AF XY: 0.144 AC XY: 10679 AN XY: 74094

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.0846

Gnomad4 ASJ AF: 0.0893

Gnomad4 EAS AF: 0.0482

Gnomad4 SAS AF: 0.0893

Gnomad4 FIN AF: 0.0578

Gnomad4 NFE AF: 0.0895

Gnomad4 OTH AF: 0.129

Alfa AF: 0.113 Hom.: 259

Bravo AF: 0.158

Asia WGS AF: 0.0990 AC: 342 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	0.41
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2227235; hg19: chr22-26326313;