19-17200417-G-A

Variant names:

Variant summary

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

The NM_004145.4(MYO9B):c.4363G>A(p.Gly1455Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 1,578,960 control chromosomes in the GnomAD database, including 1,187 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 81 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1106 hom. )

Consequence

MYO9B
NM_004145.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.721

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=0.0018480718).

BP6

Variant 19-17200417-G-A is Benign according to our data. Variant chr19-17200417-G-A is described in ClinVar as [Benign]. Clinvar id is 403217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-17200417-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0277 (4216/152304) while in subpopulation NFE AF= 0.0438 (2981/68018). AF 95% confidence interval is 0.0425. There are 81 homozygotes in gnomad4. There are 1971 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4216 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO9B	NM_004145.4 link	c.4363G>A	p.Gly1455Ser	missense_variant	Exon 25 of 40	ENST00000682292.1	NP_004136.2	Q13459-1B0I1T6Q8WVD2
MYO9B	NM_001130065.2 link	c.4363G>A	p.Gly1455Ser	missense_variant	Exon 25 of 40		NP_001123537.1	Q8WVD2Q4LE74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1 link	c.4363G>A	p.Gly1455Ser	missense_variant	Exon 25 of 40		NM_004145.4	ENSP00000507803.1		Q13459-1

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4217

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00702

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0219

Gnomad ASJ

AF:

0.0482

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.0299

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0438

Gnomad OTH

AF:

0.0321

GnomAD3 exomes

AF:

0.0297

AC:

5676

AN:

191160

Hom.:

110

AF XY:

0.0298

AC XY:

3061

AN XY:

102738

show subpopulations

Gnomad AFR exome

AF:

0.00682

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.0447

Gnomad EAS exome

AF:

0.0000732

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.0312

Gnomad NFE exome

AF:

0.0449

Gnomad OTH exome

AF:

0.0341

GnomAD4 exome

AF:

0.0377

AC:

53762

AN:

1426656

Hom.:

1106

Cov.:

AF XY:

0.0369

AC XY:

26111

AN XY:

706718

show subpopulations

Gnomad4 AFR exome

AF:

0.00597

Gnomad4 AMR exome

AF:

0.0202

Gnomad4 ASJ exome

AF:

0.0437

Gnomad4 EAS exome

AF:

0.0000786

Gnomad4 SAS exome

AF:

0.00927

Gnomad4 FIN exome

AF:

0.0303

Gnomad4 NFE exome

AF:

0.0434

Gnomad4 OTH exome

AF:

0.0308

GnomAD4 genome

AF:

0.0277

AC:

4216

AN:

152304

Hom.:

Cov.:

AF XY:

0.0265

AC XY:

1971

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00700

Gnomad4 AMR

AF:

0.0219

Gnomad4 ASJ

AF:

0.0482

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00662

Gnomad4 FIN

AF:

0.0299

Gnomad4 NFE

AF:

0.0438

Gnomad4 OTH

AF:

0.0313

Alfa

AF:

0.0395

Hom.:

179

Bravo

AF:

0.0263

TwinsUK

AF:

0.0364

AC:

135

ALSPAC

AF:

0.0389

AC:

150

ESP6500AA

AF:

0.00713

AC:

ESP6500EA

AF:

0.0397

AC:

332

ExAC

AF:

0.0244

AC:

2915

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.38

DEOGEN2

Benign

0.014

.;T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.61

.;T;T;T

MetaRNN

Benign

0.0018

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.20

N;.;N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.21

.;.;N;.

REVEL

Benign

0.15

Sift

Benign

0.76

.;.;T;.

Sift4G

Benign

0.85

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.082

MPC

0.32

ClinPred

0.000055

GERP RS

-0.36

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

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

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