rs2305764

chr19-17203024-G-Achr19-17203024-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004145.4(MYO9B):c.4879-123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,359,810 control chromosomes in the GnomAD database, including 139,241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.50 (20312 hom., cov: 33)
  • Exomes 𝑓: 0.43 (118929 hom.)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -2.49

Genes affected

MYO9B (HGNC:7609): (myosin IXB) This gene encodes a member of the myosin family of actin-based molecular motor heavy chain proteins. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-9 (MYH9). The protein has four IQ motifs located in the neck domain that bind calmodulin, which serves as a light chain. The protein complex has a single-headed structure and exhibits processive movement on actin filaments toward the minus-end. The protein also has rho-GTPase activity. Polymorphisms in this gene are associated with celiac disease and ulcerative colitis susceptibility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO9B	NM_004145.4	c.4879-123G>A		intron_variant		ENST00000682292.1
MYO9B	NM_001130065.2	c.4879-123G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO9B	ENST00000682292.1	c.4879-123G>A		intron_variant			NM_004145.4	A2

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76413 AN: 151932 Hom.: 20292 Cov.: 33

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.498

GnomAD3 exomes AF: 0.522 AC: 71446 AN: 136978 Hom.: 20147 AF XY: 0.515 AC XY: 36487 AN XY: 70822

Gnomad AFR exome AF: 0.626

Gnomad AMR exome AF: 0.701

Gnomad ASJ exome AF: 0.343

Gnomad EAS exome AF: 0.770

Gnomad SAS exome AF: 0.568

Gnomad FIN exome AF: 0.440

Gnomad NFE exome AF: 0.405

Gnomad OTH exome AF: 0.477

GnomAD4 exome AF: 0.433 AC: 522502 AN: 1207760 Hom.: 118929 Cov.: 17 AF XY: 0.436 AC XY: 259308 AN XY: 595052

Gnomad4 AFR exome AF: 0.630

Gnomad4 AMR exome AF: 0.690

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.751

Gnomad4 SAS exome AF: 0.566

Gnomad4 FIN exome AF: 0.433

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.454

GnomAD4 genome AF: 0.503 AC: 76483 AN: 152050 Hom.: 20312 Cov.: 33 AF XY: 0.508 AC XY: 37737 AN XY: 74312

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.495

Alfa AF: 0.425 Hom.: 16411

Bravo AF: 0.524

Asia WGS AF: 0.638 AC: 2217 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Celiac disease, susceptibility to, 4 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Dec 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	3.4
Dann	Benign	0.67
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs2305764; hg19: chr19-17313833;