rs12986130

Positions:

• chr19-17168942-C-A
• chr19-17168942-C-G

Variant summary

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

The NM_004145.4(MYO9B):​c.1793+878C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,032 control chromosomes in the GnomAD database, including 8,258 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 0.32 (8258 hom., cov: 32)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO9B	NM_004145.4	c.1793+878C>A		intron_variant		ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2	c.1793+878C>A		intron_variant			NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1	c.1793+878C>A		intron_variant			NM_004145.4	ENSP00000507803	A2

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49178 AN: 151914 Hom.: 8257 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.324 AC: 49200 AN: 152032 Hom.: 8258 Cov.: 32 AF XY: 0.331 AC XY: 24557 AN XY: 74298

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.353

Alfa AF: 0.330 Hom.: 5423

Bravo AF: 0.313

Asia WGS AF: 0.317 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs12986130; hg19: chr19-17279752;