19-17145656-C-T

Variant names:

• chr19-17145656-C-T
• rs17533868
• NM_004145.4:c.935+165C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004145.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO9B	NM_004145.4	MANE Select	c.935+165C>T		intron	N/A	NP_004136.2
	MYO9B	NM_001130065.2		c.935+165C>T		intron	N/A	NP_001123537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO9B	ENST00000682292.1	MANE Select	c.935+165C>T		intron	N/A	ENSP00000507803.1
	MYO9B	ENST00000595618.5	TSL:1	c.935+165C>T		intron	N/A	ENSP00000471457.1
	MYO9B	ENST00000594824.5	TSL:5	c.935+165C>T		intron	N/A	ENSP00000471367.1

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

African (AFR) AF: 0.00812 AC: 337 AN: 41500

American (AMR) AF: 0.0192 AC: 293 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0481 AC: 167 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0601 AC: 289 AN: 4806

European-Finnish (FIN) AF: 0.0311 AC: 329 AN: 10592

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0385 AC: 2618 AN: 67970

Other (OTH) AF: 0.0275 AC: 58 AN: 2112

Alfa AF: 0.0351 Hom.: 115

Bravo AF: 0.0249

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17533868; hg19: chr19-17256466;