chr19-17183487-C-T

Variant names:

• chr19-17183487-C-T
• rs2305767
• NM_004145.4:c.2334-342C>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.2334-342C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,112 control chromosomes in the GnomAD database, including 38,979 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 0.70 (38979 hom., cov: 32)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 26 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO9B	NM_004145.4	MANE Select	c.2334-342C>T		intron	N/A	NP_004136.2
	MYO9B	NM_001130065.2		c.2334-342C>T		intron	N/A	NP_001123537.1	Q13459-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO9B	ENST00000682292.1	MANE Select	c.2334-342C>T		intron	N/A	ENSP00000507803.1	Q13459-1
	MYO9B	ENST00000595618.5	TSL:1	c.2334-342C>T		intron	N/A	ENSP00000471457.1	Q13459-2
	MYO9B	ENST00000594824.5	TSL:5	c.2334-342C>T		intron	N/A	ENSP00000471367.1	M0R0P8

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106539 AN: 151994 Hom.: 38927 Cov.: 32

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.701 AC: 106645 AN: 152112 Hom.: 38979 Cov.: 32 AF XY: 0.701 AC XY: 52144 AN XY: 74362

African (AFR) AF: 0.918 AC: 38113 AN: 41536

American (AMR) AF: 0.738 AC: 11267 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1694 AN: 3470

East Asian (EAS) AF: 0.740 AC: 3820 AN: 5164

South Asian (SAS) AF: 0.654 AC: 3153 AN: 4822

European-Finnish (FIN) AF: 0.617 AC: 6532 AN: 10584

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39945 AN: 67946

Other (OTH) AF: 0.681 AC: 1438 AN: 2112

Alfa AF: 0.629 Hom.: 100366

Bravo AF: 0.724

Asia WGS AF: 0.685 AC: 2380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.36
PhyloP100		-1.7
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: rs2305767; hg19: chr19-17294296;