NM_004145.4:c.840+16920A>C

Variant names:

• chr19-17119477-A-C
• rs8099879
• NM_004145.4:c.840+16920A>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.840+16920A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 151,986 control chromosomes in the GnomAD database, including 34,839 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 0.67 (34839 hom., cov: 32)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 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.840+16920A>C		intron	N/A	NP_004136.2
	MYO9B	NM_001130065.2		c.840+16920A>C		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.840+16920A>C		intron	N/A	ENSP00000507803.1
	MYO9B	ENST00000595618.5	TSL:1	c.840+16920A>C		intron	N/A	ENSP00000471457.1
	MYO9B	ENST00000594824.5	TSL:5	c.840+16920A>C		intron	N/A	ENSP00000471367.1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102110 AN: 151868 Hom.: 34798 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.672 AC: 102206 AN: 151986 Hom.: 34839 Cov.: 32 AF XY: 0.668 AC XY: 49645 AN XY: 74282

African (AFR) AF: 0.775 AC: 32119 AN: 41432

American (AMR) AF: 0.572 AC: 8736 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2351 AN: 3472

East Asian (EAS) AF: 0.849 AC: 4377 AN: 5158

South Asian (SAS) AF: 0.522 AC: 2516 AN: 4818

European-Finnish (FIN) AF: 0.669 AC: 7081 AN: 10582

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.631 AC: 42864 AN: 67940

Other (OTH) AF: 0.656 AC: 1387 AN: 2114

Alfa AF: 0.624 Hom.: 23896

Bravo AF: 0.674

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.55
PhyloP100		-0.0050
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: rs8099879; hg19: chr19-17230287;