19-17102179-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_004145.4(MYO9B):c.462C>T(p.Leu154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,613,874 control chromosomes in the GnomAD database, including 264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 7 hom., cov: 32)

Exomes 𝑓: 0.016 ( 257 hom. )

Consequence

MYO9B
NM_004145.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.03

Variant links:

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]

MYO9B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 19-17102179-C-T is Benign according to our data. Variant chr19-17102179-C-T is described in ClinVar as [Benign]. Clinvar id is 3037288.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.03 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0106 (1616/152336) while in subpopulation NFE AF= 0.0186 (1265/68026). AF 95% confidence interval is 0.0177. There are 7 homozygotes in gnomad4. There are 770 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd at 1615 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO9B	NM_004145.4 linkuse as main transcript	c.462C>T	p.Leu154=	synonymous_variant	2/40	ENST00000682292.1
MYO9B	NM_001130065.2 linkuse as main transcript	c.462C>T	p.Leu154=	synonymous_variant	2/40

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO9B	ENST00000682292.1 linkuse as main transcript	c.462C>T	p.Leu154=	synonymous_variant	2/40		NM_004145.4	A2	Q13459-1

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1615

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00311

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00621

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00744

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00963

AC:

2397

AN:

248990

Hom.:

AF XY:

0.00985

AC XY:

1331

AN XY:

135118

show subpopulations

Gnomad AFR exome

AF:

0.00258

Gnomad AMR exome

AF:

0.00261

Gnomad ASJ exome

AF:

0.00249

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00232

Gnomad FIN exome

AF:

0.00772

Gnomad NFE exome

AF:

0.0173

Gnomad OTH exome

AF:

0.00860

GnomAD4 exome

AF:

0.0158

AC:

23097

AN:

1461538

Hom.:

257

Cov.:

AF XY:

0.0154

AC XY:

11226

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.00221

Gnomad4 AMR exome

AF:

0.00313

Gnomad4 ASJ exome

AF:

0.00310

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00260

Gnomad4 FIN exome

AF:

0.00866

Gnomad4 NFE exome

AF:

0.0191

Gnomad4 OTH exome

AF:

0.0139

GnomAD4 genome

AF:

0.0106

AC:

1616

AN:

152336

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

770

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00310

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00744

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.0142

Hom.:

Bravo

AF:

0.00998

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0154

EpiControl

AF:

0.0162

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MYO9B-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

Cadd

Benign

5.2

Dann

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over