rs8107108

Positions:

• chr19-17200499-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004145.4(MYO9B):​c.4372+73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 1,519,530 control chromosomes in the GnomAD database, including 4,786 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 0.090 (728 hom., cov: 32)
  • Exomes 𝑓: 0.074 (4058 hom.)
• Consequence: MYO9B NM_004145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO9B	NM_004145.4	c.4372+73C>T		intron_variant		ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2	c.4372+73C>T		intron_variant			NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1	c.4372+73C>T		intron_variant			NM_004145.4	ENSP00000507803	A2

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13740 AN: 152072 Hom.: 724 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0573

Gnomad AMR AF: 0.0658

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.0840

GnomAD4 exome AF: 0.0737 AC: 100791 AN: 1367340 Hom.: 4058 Cov.: 31 AF XY: 0.0717 AC XY: 48273 AN XY: 672846

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0513

Gnomad4 ASJ exome AF: 0.0617

Gnomad4 EAS exome AF: 0.000112

Gnomad4 SAS exome AF: 0.0181

Gnomad4 FIN exome AF: 0.0765

Gnomad4 NFE exome AF: 0.0789

Gnomad4 OTH exome AF: 0.0730

GnomAD4 genome AF: 0.0904 AC: 13755 AN: 152190 Hom.: 728 Cov.: 32 AF XY: 0.0875 AC XY: 6513 AN XY: 74408

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.0656

Gnomad4 ASJ AF: 0.0611

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.0732

Gnomad4 NFE AF: 0.0791

Gnomad4 OTH AF: 0.0822

Alfa AF: 0.0766 Hom.: 697

Bravo AF: 0.0925

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs8107108; hg19: chr19-17311308;