19-17145656-C-T

Variant summary

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

The NM_004145.4(MYO9B):c.935+165C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 152,090 control chromosomes in the GnomAD database, including 97 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 0.028 (97 hom., cov: 32)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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 (SAS) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO9B	NM_004145.4	c.935+165C>T		intron_variant		ENST00000682292.1
MYO9B	NM_001130065.2	c.935+165C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO9B	ENST00000682292.1	c.935+165C>T		intron_variant			NM_004145.4	A2

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4297 AN: 151972 Hom.: 97 Cov.: 32

Gnomad AFR AF: 0.00812

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0595

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0385

Gnomad OTH AF: 0.0278

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

GnomAD4 genome AF: 0.0283 AC: 4301 AN: 152090 Hom.: 97 Cov.: 32 AF XY: 0.0285 AC XY: 2119 AN XY: 74346

Gnomad4 AFR AF: 0.00812

Gnomad4 AMR AF: 0.0192

Gnomad4 ASJ AF: 0.0481

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0601

Gnomad4 FIN AF: 0.0311

Gnomad4 NFE AF: 0.0385

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0370 Hom.: 26

Bravo AF: 0.0249

Asia WGS AF: 0.0230 AC: 80 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	1.2
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs17533868; hg19: chr19-17256466;