chr19-17146992-T-C

Variant names:

• chr19-17146992-T-C
• rs17533945
• NM_004145.4:c.935+1501T>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.935+1501T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,182 control chromosomes in the GnomAD database, including 18,792 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 0.48 (18792 hom., cov: 33)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 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.935+1501T>C		intron	N/A	NP_004136.2
	MYO9B	NM_001130065.2		c.935+1501T>C		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.935+1501T>C		intron	N/A	ENSP00000507803.1	Q13459-1
	MYO9B	ENST00000595618.5	TSL:1	c.935+1501T>C		intron	N/A	ENSP00000471457.1	Q13459-2
	MYO9B	ENST00000594824.5	TSL:5	c.935+1501T>C		intron	N/A	ENSP00000471367.1	M0R0P8

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72724 AN: 152064 Hom.: 18765 Cov.: 33

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.478 AC: 72798 AN: 152182 Hom.: 18792 Cov.: 33 AF XY: 0.478 AC XY: 35540 AN XY: 74380

African (AFR) AF: 0.684 AC: 28398 AN: 41528

American (AMR) AF: 0.416 AC: 6359 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1014 AN: 3472

East Asian (EAS) AF: 0.367 AC: 1898 AN: 5170

South Asian (SAS) AF: 0.363 AC: 1753 AN: 4834

European-Finnish (FIN) AF: 0.487 AC: 5153 AN: 10580

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26780 AN: 67990

Other (OTH) AF: 0.434 AC: 917 AN: 2112

Alfa AF: 0.413 Hom.: 8162

Bravo AF: 0.482

Asia WGS AF: 0.378 AC: 1317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.4
DANN	Benign	0.39
PhyloP100		0.34
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: rs17533945; hg19: chr19-17257802;