chr19-17128756-G-A

Variant names:

• chr19-17128756-G-A
• rs7254359
• NM_004145.4:c.841-16641G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004145.4(MYO9B):​c.841-16641G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,140 control chromosomes in the GnomAD database, including 18,563 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 0.49 (18563 hom., cov: 33)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.495 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.841-16641G>A		intron	N/A	NP_004136.2
	MYO9B	NM_001130065.2		c.841-16641G>A		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.841-16641G>A		intron	N/A	ENSP00000507803.1
	MYO9B	ENST00000595618.5	TSL:1	c.841-16641G>A		intron	N/A	ENSP00000471457.1
	MYO9B	ENST00000594824.5	TSL:5	c.841-16641G>A		intron	N/A	ENSP00000471367.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74847 AN: 152022 Hom.: 18570 Cov.: 33

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.492 AC: 74861 AN: 152140 Hom.: 18563 Cov.: 33 AF XY: 0.498 AC XY: 37006 AN XY: 74364

African (AFR) AF: 0.472 AC: 19612 AN: 41510

American (AMR) AF: 0.472 AC: 7210 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1428 AN: 3470

East Asian (EAS) AF: 0.485 AC: 2509 AN: 5168

South Asian (SAS) AF: 0.470 AC: 2269 AN: 4832

European-Finnish (FIN) AF: 0.609 AC: 6449 AN: 10588

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33964 AN: 67988

Other (OTH) AF: 0.449 AC: 950 AN: 2114

Alfa AF: 0.491 Hom.: 54408

Bravo AF: 0.481

Asia WGS AF: 0.469 AC: 1630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.87
PhyloP100		0.56
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: rs7254359; hg19: chr19-17239566;