rs1001021

Variant names:

• chr22-26007633-G-A
• rs1001021
• NM_032608.7:c.6470+2778G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-26007633-G-A
• chr22-26007633-G-C
• chr22-26007633-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032608.7(MYO18B):​c.6470+2778G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0595 in 152,226 control chromosomes in the GnomAD database, including 527 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 0.059 (527 hom., cov: 32)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.6470+2778G>A		intron_variant	Intron 42 of 43	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.6470+2778G>A		intron_variant	Intron 42 of 43	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.6473+2778G>A		intron_variant	Intron 42 of 43	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.6470+2778G>A		intron_variant	Intron 42 of 42	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.*3928+2778G>A		intron_variant	Intron 40 of 41	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9051 AN: 152108 Hom.: 527 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.0685

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0444

Gnomad OTH AF: 0.0791

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

GnomAD4 genome AF: 0.0595 AC: 9056 AN: 152226 Hom.: 527 Cov.: 32 AF XY: 0.0663 AC XY: 4931 AN XY: 74424

African (AFR) AF: 0.0118 AC: 489 AN: 41554

American (AMR) AF: 0.167 AC: 2547 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0911 AC: 316 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1044 AN: 5186

South Asian (SAS) AF: 0.0683 AC: 329 AN: 4816

European-Finnish (FIN) AF: 0.105 AC: 1107 AN: 10574

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

European-Non Finnish (NFE) AF: 0.0444 AC: 3018 AN: 68026

Other (OTH) AF: 0.0778 AC: 164 AN: 2108

Alfa AF: 0.0556 Hom.: 713

Bravo AF: 0.0629

Asia WGS AF: 0.115 AC: 401 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.95
DANN	Benign	0.49
PhyloP100		0.043
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: rs1001021; hg19: chr22-26403599;