NM_032608.7:c.39+211G>C

Variant names:

• chr22-25761342-G-C
• rs133878
• NM_032608.7:c.39+211G>C

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.39+211G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (331 hom., cov: 0)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.71
• Publications: 1 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=-0.97).
• BP6: Variant 22-25761342-G-C is Benign according to our data. Variant chr22-25761342-G-C is described in ClinVar as [Benign]. Clinvar id is 1256908.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.39+211G>C		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+211G>C		intron_variant	Intron 2 of 43	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.39+211G>C		intron_variant	Intron 2 of 43	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.39+211G>C		intron_variant	Intron 2 of 42	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.39+211G>C		intron_variant	Intron 1 of 41	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 5490 AN: 41770 Hom.: 331 Cov.: 0

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0608

Gnomad ASJ AF: 0.00123

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.0218

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0196

Gnomad NFE AF: 0.00208

Gnomad OTH AF: 0.0907

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

GnomAD4 genome AF: 0.132 AC: 5503 AN: 41792 Hom.: 331 Cov.: 0 AF XY: 0.129 AC XY: 2604 AN XY: 20188

African (AFR) AF: 0.484 AC: 5142 AN: 10628

American (AMR) AF: 0.0608 AC: 178 AN: 2926

Ashkenazi Jewish (ASJ) AF: 0.00123 AC: 1 AN: 814

East Asian (EAS) AF: 0.230 AC: 65 AN: 282

South Asian (SAS) AF: 0.0219 AC: 21 AN: 960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3434

Middle Eastern (MID) AF: 0.0213 AC: 2 AN: 94

European-Non Finnish (NFE) AF: 0.00208 AC: 45 AN: 21638

Other (OTH) AF: 0.0901 AC: 49 AN: 544

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 13, 2021

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	-0.97
CADD	Benign	0.33
DANN	Benign	0.24
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: rs133878; hg19: chr22-26157309;