rs2279006

Variant names:

• chr19-17172848-C-T
• rs2279006
• NM_004145.4:c.2025C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004145.4(MYO9B):​c.2025C>T​(p.Ile675Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0861 in 1,610,452 control chromosomes in the GnomAD database, including 7,648 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 0.13 (1908 hom., cov: 32)
  • Exomes 𝑓: 0.081 (5740 hom.)
• Consequence: MYO9B NM_004145.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.76
• Publications: 19 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-4.76 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO9B	NM_004145.4	c.2025C>T	p.Ile675Ile	synonymous_variant	Exon 13 of 40	ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2	c.2025C>T	p.Ile675Ile	synonymous_variant	Exon 13 of 40		NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1	c.2025C>T	p.Ile675Ile	synonymous_variant	Exon 13 of 40		NM_004145.4	ENSP00000507803.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19947 AN: 152026 Hom.: 1905 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0765

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.0967

Gnomad SAS AF: 0.0709

Gnomad FIN AF: 0.0693

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0760

Gnomad OTH AF: 0.120

GnomAD2 exomes AF: 0.0892 AC: 21814 AN: 244442 AF XY: 0.0868

Gnomad AFR exome AF: 0.284

Gnomad AMR exome AF: 0.0609

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.0854

Gnomad FIN exome AF: 0.0749

Gnomad NFE exome AF: 0.0772

Gnomad OTH exome AF: 0.0928

GnomAD4 exome AF: 0.0814 AC: 118733 AN: 1458308 Hom.: 5740 Cov.: 33 AF XY: 0.0809 AC XY: 58728 AN XY: 725624

African (AFR) AF: 0.284 AC: 9506 AN: 33476

American (AMR) AF: 0.0631 AC: 2823 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 2827 AN: 26128

East Asian (EAS) AF: 0.107 AC: 4230 AN: 39696

South Asian (SAS) AF: 0.0710 AC: 6128 AN: 86254

European-Finnish (FIN) AF: 0.0773 AC: 3878 AN: 50146

Middle Eastern (MID) AF: 0.144 AC: 833 AN: 5768

European-Non Finnish (NFE) AF: 0.0746 AC: 82971 AN: 1111780

Other (OTH) AF: 0.0918 AC: 5537 AN: 60340

GnomAD4 genome AF: 0.131 AC: 19968 AN: 152144 Hom.: 1908 Cov.: 32 AF XY: 0.127 AC XY: 9458 AN XY: 74400

African (AFR) AF: 0.275 AC: 11410 AN: 41480

American (AMR) AF: 0.0763 AC: 1166 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 345 AN: 3470

East Asian (EAS) AF: 0.0964 AC: 498 AN: 5168

South Asian (SAS) AF: 0.0705 AC: 340 AN: 4822

European-Finnish (FIN) AF: 0.0693 AC: 735 AN: 10610

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0760 AC: 5165 AN: 67998

Other (OTH) AF: 0.118 AC: 250 AN: 2114

Alfa AF: 0.0899 Hom.: 1457

Bravo AF: 0.140

Asia WGS AF: 0.0970 AC: 337 AN: 3478

EpiCase AF: 0.0767

EpiControl AF: 0.0804

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.3
DANN	Benign	0.80
PhyloP100		-4.8
PromoterAI		-0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=79/21	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: rs2279006; hg19: chr19-17283657; COSMIC: COSV68279484; COSMIC: COSV68279484;