22-25761332-T-C

Position:

• chr22-25761332-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032608.7(MYO18B):​c.39+201T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 137,652 control chromosomes in the GnomAD database, including 4,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (4776 hom., cov: 32)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0520

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-25761332-T-C is Benign according to our data. Variant chr22-25761332-T-C is described in ClinVar as [Benign]. Clinvar id is 1291686.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO18B	NM_032608.7	c.39+201T>C		intron_variant		ENST00000335473.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO18B	ENST00000335473.12	c.39+201T>C		intron_variant		1	NM_032608.7	A2
MYO18B	ENST00000407587.6	c.39+201T>C		intron_variant		1		P5
MYO18B	ENST00000536101.5	c.39+201T>C		intron_variant		1		A2
MYO18B	ENST00000539302.5	c.39+201T>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 36902 AN: 137578 Hom.: 4759 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.268 AC: 36944 AN: 137652 Hom.: 4776 Cov.: 32 AF XY: 0.265 AC XY: 17694 AN XY: 66768

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.270

Alfa AF: 0.231 Hom.: 844

Bravo AF: 0.257

Asia WGS AF: 0.155 AC: 539 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6004758; hg19: chr22-26157299;