rs2227235

Variant names:

• chr22-25930346-T-C
• rs2227235
• NM_032608.7:c.5517+8937T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-25930346-T-C
• chr22-25930346-T-G

Variant summary

Our verdict is Benign. The variant received -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
• 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 (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.5517+8937T>C		intron_variant	Intron 34 of 43	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.5517+8937T>C		intron_variant	Intron 34 of 43	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.5520+8937T>C		intron_variant	Intron 34 of 43	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.5517+8937T>C		intron_variant	Intron 34 of 42	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.*2975+8937T>C		intron_variant	Intron 32 of 41	1		ENSP00000437587.1

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

African (AFR) AF: 0.318 AC: 13118 AN: 41254

American (AMR) AF: 0.0846 AC: 1287 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3470

East Asian (EAS) AF: 0.0482 AC: 246 AN: 5108

South Asian (SAS) AF: 0.0893 AC: 429 AN: 4802

European-Finnish (FIN) AF: 0.0578 AC: 610 AN: 10548

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0895 AC: 6076 AN: 67918

Other (OTH) AF: 0.129 AC: 272 AN: 2106

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
PhyloP100		-1.3
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: rs2227235; hg19: chr22-26326313;