chr19-17191438-G-A

Variant names:

• chr19-17191438-G-A
• rs962917
• NM_004145.4:c.2811+219G>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.2811+219G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,982 control chromosomes in the GnomAD database, including 16,214 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 (16214 hom., cov: 31)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727
• Publications: 21 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO9B	NM_004145.4	c.2811+219G>A		intron_variant	Intron 20 of 39	ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2	c.2811+219G>A		intron_variant	Intron 20 of 39		NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1	c.2811+219G>A		intron_variant	Intron 20 of 39		NM_004145.4	ENSP00000507803.1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68304 AN: 151864 Hom.: 16202 Cov.: 31

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.450 AC: 68351 AN: 151982 Hom.: 16214 Cov.: 31 AF XY: 0.456 AC XY: 33899 AN XY: 74276

African (AFR) AF: 0.519 AC: 21515 AN: 41446

American (AMR) AF: 0.573 AC: 8746 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1047 AN: 3468

East Asian (EAS) AF: 0.737 AC: 3798 AN: 5156

South Asian (SAS) AF: 0.547 AC: 2637 AN: 4818

European-Finnish (FIN) AF: 0.429 AC: 4533 AN: 10570

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.363 AC: 24663 AN: 67940

Other (OTH) AF: 0.458 AC: 968 AN: 2114

Alfa AF: 0.401 Hom.: 33400

Bravo AF: 0.470

Asia WGS AF: 0.594 AC: 2063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.064
DANN	Benign	0.45
PhyloP100		-0.73
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: rs962917; hg19: chr19-17302247;