rs1457092

Variant names:

• chr19-17193427-C-A
• rs1457092
• NM_004145.4:c.3128+365C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-17193427-C-A
• chr19-17193427-C-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.3128+365C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,880 control chromosomes in the GnomAD database, including 15,928 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 0.45 (15928 hom., cov: 31)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 20 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 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.3128+365C>A		intron	N/A	NP_004136.2
	MYO9B	NM_001130065.2		c.3128+365C>A		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.3128+365C>A		intron	N/A	ENSP00000507803.1	Q13459-1
	MYO9B	ENST00000595618.5	TSL:1	c.3128+365C>A		intron	N/A	ENSP00000471457.1	Q13459-2
	MYO9B	ENST00000594824.5	TSL:5	c.3128+365C>A		intron	N/A	ENSP00000471367.1	M0R0P8

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67606 AN: 151762 Hom.: 15916 Cov.: 31

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.445 AC: 67652 AN: 151880 Hom.: 15928 Cov.: 31 AF XY: 0.452 AC XY: 33587 AN XY: 74234

African (AFR) AF: 0.500 AC: 20702 AN: 41410

American (AMR) AF: 0.572 AC: 8726 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1047 AN: 3472

East Asian (EAS) AF: 0.758 AC: 3899 AN: 5144

South Asian (SAS) AF: 0.549 AC: 2643 AN: 4810

European-Finnish (FIN) AF: 0.429 AC: 4532 AN: 10560

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.364 AC: 24701 AN: 67920

Other (OTH) AF: 0.455 AC: 960 AN: 2110

Alfa AF: 0.381 Hom.: 4883

Bravo AF: 0.465

Asia WGS AF: 0.600 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-0.13
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: rs1457092; hg19: chr19-17304236;