19-17206443-A-G

Variant summary

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

The NM_004145.4(MYO9B):c.5386+67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,565,702 control chromosomes in the GnomAD database, including 106,512 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 0.39 (12572 hom., cov: 33)
  • Exomes 𝑓: 0.35 (93940 hom.)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO9B	NM_004145.4	c.5386+67A>G		intron_variant		ENST00000682292.1
MYO9B	NM_001130065.2	c.5386+67A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO9B	ENST00000682292.1	c.5386+67A>G		intron_variant			NM_004145.4	A2

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59597 AN: 152022 Hom.: 12561 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.393

GnomAD4 exome AF: 0.351 AC: 495986 AN: 1413562 Hom.: 93940 AF XY: 0.352 AC XY: 245895 AN XY: 699442

Gnomad4 AFR exome AF: 0.447

Gnomad4 AMR exome AF: 0.646

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.757

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.361

GnomAD4 genome AF: 0.392 AC: 59625 AN: 152140 Hom.: 12572 Cov.: 33 AF XY: 0.398 AC XY: 29603 AN XY: 74370

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.392

Alfa AF: 0.256 Hom.: 1174

Bravo AF: 0.410

Asia WGS AF: 0.559 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.11
Dann	Benign	0.50

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: rs2279002; hg19: chr19-17317252;