chr19-17135402-T-C

Variant names:

• chr19-17135402-T-C
• rs10423232
• NM_004145.4:c.841-9995T>C

Variant summary

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

The NM_004145.4(MYO9B):​c.841-9995T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,812 control chromosomes in the GnomAD database, including 6,422 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 0.27 (6422 hom., cov: 31)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• Publications: 7 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO9B	NM_004145.4	c.841-9995T>C		intron_variant	Intron 2 of 39	ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2	c.841-9995T>C		intron_variant	Intron 2 of 39		NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1	c.841-9995T>C		intron_variant	Intron 2 of 39		NM_004145.4	ENSP00000507803.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40187 AN: 151694 Hom.: 6399 Cov.: 31

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.265 AC: 40270 AN: 151812 Hom.: 6422 Cov.: 31 AF XY: 0.260 AC XY: 19298 AN XY: 74200

African (AFR) AF: 0.454 AC: 18772 AN: 41348

American (AMR) AF: 0.213 AC: 3247 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3468

East Asian (EAS) AF: 0.287 AC: 1477 AN: 5144

South Asian (SAS) AF: 0.152 AC: 732 AN: 4810

European-Finnish (FIN) AF: 0.160 AC: 1690 AN: 10562

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12836 AN: 67944

Other (OTH) AF: 0.258 AC: 545 AN: 2112

Alfa AF: 0.213 Hom.: 12317

Bravo AF: 0.279

Asia WGS AF: 0.223 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.2
DANN	Benign	0.68
PhyloP100		0.14
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: rs10423232; hg19: chr19-17246212;