19-17101884-G-A

Position:

chr19-17101884-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004145.4(MYO9B):c.167G>A(p.Arg56Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,613,414 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 32 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 24 hom. )

Consequence

MYO9B
NM_004145.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.124

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036690235).

BP6

Variant 19-17101884-G-A is Benign according to our data. Variant chr19-17101884-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 781444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1631/152280) while in subpopulation AFR AF= 0.0376 (1562/41546). AF 95% confidence interval is 0.036. There are 32 homozygotes in gnomad4. There are 743 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1631 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO9B	NM_004145.4 linkuse as main transcript	c.167G>A	p.Arg56Gln	missense_variant	2/40	ENST00000682292.1	NP_004136.2	Q13459-1B0I1T6Q8WVD2
MYO9B	NM_001130065.2 linkuse as main transcript	c.167G>A	p.Arg56Gln	missense_variant	2/40		NP_001123537.1	Q8WVD2Q4LE74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1 linkuse as main transcript	c.167G>A	p.Arg56Gln	missense_variant	2/40		NM_004145.4	ENSP00000507803.1		Q13459-1

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1628

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0376

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00248

AC:

615

AN:

247610

Hom.:

AF XY:

0.00199

AC XY:

268

AN XY:

134640

show subpopulations

Gnomad AFR exome

AF:

0.0354

Gnomad AMR exome

AF:

0.00128

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000205

Gnomad OTH exome

AF:

0.000498

GnomAD4 exome

AF:

0.00111

AC:

1621

AN:

1461134

Hom.:

Cov.:

AF XY:

0.000973

AC XY:

707

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.0396

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000854

Gnomad4 OTH exome

AF:

0.00207

GnomAD4 genome

AF:

0.0107

AC:

1631

AN:

152280

Hom.:

Cov.:

AF XY:

0.00998

AC XY:

743

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0376

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00228

Hom.:

Bravo

AF:

0.0120

ESP6500AA

AF:

0.0332

AC:

141

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00323

AC:

391

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MYO9B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 20, 2020

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). -

Celiac disease, susceptibility to, 4

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 13, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.81

DANN

Benign

0.96

DEOGEN2

Benign

0.0079

.;T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.75

.;T;T;T

MetaRNN

Benign

0.0037

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.41

N;.;N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

0.060

.;.;N;.

REVEL

Benign

0.043

Sift

Benign

0.71

.;.;T;.

Sift4G

Benign

0.57

T;T;T;T

Vest4

0.067

MVP

0.32

MPC

0.84

ClinPred

0.0030

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.22

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