19-17202183-C-T

Variant names:

• chr19-17202183-C-T
• rs2305765
• NM_004145.4:c.4716C>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.4716C>T​(p.Val1572Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 1,612,976 control chromosomes in the GnomAD database, including 164,763 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 0.49 (18986 hom., cov: 31)
  • Exomes 𝑓: 0.44 (145777 hom.)
• Consequence: MYO9B NM_004145.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848
• Publications: 29 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=-0.53).
• BP7: Synonymous conserved (PhyloP=-0.848 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO9B	NM_004145.4	c.4716C>T	p.Val1572Val	synonymous_variant	Exon 28 of 40	ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2	c.4716C>T	p.Val1572Val	synonymous_variant	Exon 28 of 40		NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1	c.4716C>T	p.Val1572Val	synonymous_variant	Exon 28 of 40		NM_004145.4	ENSP00000507803.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74215 AN: 151862 Hom.: 18970 Cov.: 31

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.489

GnomAD2 exomes AF: 0.504 AC: 124845 AN: 247912 AF XY: 0.493

Gnomad AFR exome AF: 0.571

Gnomad AMR exome AF: 0.716

Gnomad ASJ exome AF: 0.337

Gnomad EAS exome AF: 0.774

Gnomad FIN exome AF: 0.441

Gnomad NFE exome AF: 0.399

Gnomad OTH exome AF: 0.472

GnomAD4 exome AF: 0.437 AC: 638362 AN: 1460996 Hom.: 145777 Cov.: 51 AF XY: 0.439 AC XY: 319269 AN XY: 726728

African (AFR) AF: 0.585 AC: 19596 AN: 33470

American (AMR) AF: 0.703 AC: 31366 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 8721 AN: 26114

East Asian (EAS) AF: 0.754 AC: 29908 AN: 39690

South Asian (SAS) AF: 0.568 AC: 48963 AN: 86178

European-Finnish (FIN) AF: 0.434 AC: 23136 AN: 53316

Middle Eastern (MID) AF: 0.470 AC: 2711 AN: 5764

European-Non Finnish (NFE) AF: 0.402 AC: 446569 AN: 1111518

Other (OTH) AF: 0.454 AC: 27392 AN: 60340

GnomAD4 genome AF: 0.489 AC: 74280 AN: 151980 Hom.: 18986 Cov.: 31 AF XY: 0.494 AC XY: 36709 AN XY: 74262

African (AFR) AF: 0.571 AC: 23682 AN: 41460

American (AMR) AF: 0.594 AC: 9070 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1177 AN: 3472

East Asian (EAS) AF: 0.762 AC: 3926 AN: 5150

South Asian (SAS) AF: 0.597 AC: 2876 AN: 4818

European-Finnish (FIN) AF: 0.451 AC: 4767 AN: 10572

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27298 AN: 67932

Other (OTH) AF: 0.486 AC: 1024 AN: 2106

Alfa AF: 0.427 Hom.: 26803

Bravo AF: 0.508

Asia WGS AF: 0.637 AC: 2212 AN: 3478

EpiCase AF: 0.402

EpiControl AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.5
DANN	Benign	0.71
PhyloP100		-0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs2305765; hg19: chr19-17312992; COSMIC: COSV108244498; COSMIC: COSV108244498;