rs7259292

Variant names:

• chr19-17181205-C-T
• rs7259292
• NM_004145.4:c.2333+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.2333+165C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 152,280 control chromosomes in the GnomAD database, including 808 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 0.075 (808 hom., cov: 32)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO9B	NM_004145.4	c.2333+165C>T		intron_variant	Intron 15 of 39	ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2	c.2333+165C>T		intron_variant	Intron 15 of 39		NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1	c.2333+165C>T		intron_variant	Intron 15 of 39		NM_004145.4	ENSP00000507803.1

Frequencies

GnomAD3 genomes AF: 0.0744 AC: 11322 AN: 152162 Hom.: 803 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00910

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0350

Gnomad OTH AF: 0.0621

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

GnomAD4 genome AF: 0.0746 AC: 11355 AN: 152280 Hom.: 808 Cov.: 32 AF XY: 0.0721 AC XY: 5368 AN XY: 74460

African (AFR) AF: 0.187 AC: 7755 AN: 41532

American (AMR) AF: 0.0512 AC: 783 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00870 AC: 42 AN: 4830

European-Finnish (FIN) AF: 0.0121 AC: 128 AN: 10614

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0350 AC: 2382 AN: 68024

Other (OTH) AF: 0.0614 AC: 130 AN: 2116

Alfa AF: 0.0421 Hom.: 394

Bravo AF: 0.0816

Asia WGS AF: 0.0180 AC: 65 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	0.79
DANN	Benign	0.44
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs7259292; hg19: chr19-17292014;