NM_032608.7:c.6287+247G>A

Variant names:

• chr22-25992740-G-A
• rs5752249
• NM_032608.7:c.6287+247G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032608.7(MYO18B):​c.6287+247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 152,282 control chromosomes in the GnomAD database, including 656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.063 (656 hom., cov: 33)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0110
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-25992740-G-A is Benign according to our data. Variant chr22-25992740-G-A is described in ClinVar as [Benign]. Clinvar id is 1231212.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.6287+247G>A		intron_variant	Intron 40 of 43	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.6287+247G>A		intron_variant	Intron 40 of 43	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.6290+247G>A		intron_variant	Intron 40 of 43	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.6287+247G>A		intron_variant	Intron 40 of 42	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.*3745+247G>A		intron_variant	Intron 38 of 41	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9645 AN: 152164 Hom.: 655 Cov.: 33

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0453

Gnomad OTH AF: 0.0832

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

GnomAD4 genome AF: 0.0634 AC: 9651 AN: 152282 Hom.: 656 Cov.: 33 AF XY: 0.0701 AC XY: 5221 AN XY: 74450

African (AFR) AF: 0.0130 AC: 539 AN: 41582

American (AMR) AF: 0.194 AC: 2969 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0813 AC: 282 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1217 AN: 5160

South Asian (SAS) AF: 0.0695 AC: 335 AN: 4822

European-Finnish (FIN) AF: 0.0953 AC: 1011 AN: 10610

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0453 AC: 3083 AN: 68022

Other (OTH) AF: 0.0818 AC: 173 AN: 2114

Alfa AF: 0.0606 Hom.: 731

Bravo AF: 0.0701

Asia WGS AF: 0.128 AC: 445 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.39
PhyloP100		0.011
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: rs5752249; hg19: chr22-26388706;