19-17188084-G-T

Position:

• chr19-17188084-G-T

Variant summary

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

The NM_004145.4(MYO9B):​c.2688+39G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,511,012 control chromosomes in the GnomAD database, including 159,606 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 0.53 (23370 hom., cov: 31)
  • Exomes 𝑓: 0.44 (136236 hom.)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO9B	NM_004145.4	c.2688+39G>T		intron_variant		ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2	c.2688+39G>T		intron_variant			NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1	c.2688+39G>T		intron_variant			NM_004145.4	ENSP00000507803.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80818 AN: 151762 Hom.: 23338 Cov.: 31

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.527

GnomAD3 exomes AF: 0.512 AC: 81405 AN: 159120 Hom.: 22598 AF XY: 0.503 AC XY: 42332 AN XY: 84160

Gnomad AFR exome AF: 0.741

Gnomad AMR exome AF: 0.714

Gnomad ASJ exome AF: 0.336

Gnomad EAS exome AF: 0.739

Gnomad SAS exome AF: 0.532

Gnomad FIN exome AF: 0.426

Gnomad NFE exome AF: 0.400

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.437 AC: 593863 AN: 1359132 Hom.: 136236 Cov.: 21 AF XY: 0.439 AC XY: 294207 AN XY: 670320

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.704

Gnomad4 ASJ exome AF: 0.327

Gnomad4 EAS exome AF: 0.733

Gnomad4 SAS exome AF: 0.543

Gnomad4 FIN exome AF: 0.421

Gnomad4 NFE exome AF: 0.402

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.533 AC: 80900 AN: 151880 Hom.: 23370 Cov.: 31 AF XY: 0.536 AC XY: 39799 AN XY: 74200

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.524

Alfa AF: 0.399 Hom.: 8416

Bravo AF: 0.560

Asia WGS AF: 0.613 AC: 2129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.068
DANN	Benign	0.56

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: rs3826689; hg19: chr19-17298893;