chr18-49929553-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001080467.3(MYO5B):c.2049G>A(p.Val683Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,605,794 control chromosomes in the GnomAD database, including 226,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18337 hom., cov: 26)

Exomes 𝑓: 0.53 ( 208650 hom. )

Consequence

MYO5B
NM_001080467.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.208

Publications

15 publications found

Variant links:

Genes affected

MYO5B (HGNC:7603): (myosin VB) The protein encoded by this gene, together with other proteins, may be involved in plasma membrane recycling. Mutations in this gene are associated with microvillous inclusion disease. [provided by RefSeq, Sep 2009]

MYO5B Gene-Disease associations (from GenCC):

microvillus inclusion disease
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
cholestasis, progressive familial intrahepatic, 10
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
progressive familial intrahepatic cholestasis type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MYO5B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 18-49929553-C-T is Benign according to our data. Variant chr18-49929553-C-T is described in ClinVar as Benign. ClinVar VariationId is 327053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.208 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3 link	c.2049G>A	p.Val683Val	synonymous_variant	Exon 17 of 40	ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12 link	c.2049G>A	p.Val683Val	synonymous_variant	Exon 17 of 40	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1 link	c.1845G>A	p.Val615Val	synonymous_variant	Exon 15 of 38			ENSP00000513188.1

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

72853

AN:

149870

Hom.:

18340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.411

Gnomad AMI

AF:

0.728

Gnomad AMR

AF:

0.409

Gnomad ASJ

AF:

0.587

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.504

GnomAD2 exomes

AF:

0.468

AC:

114072

AN:

243844

AF XY:

0.480

show subpopulations

Gnomad AFR exome

AF:

0.403

Gnomad AMR exome

AF:

0.312

Gnomad ASJ exome

AF:

0.589

Gnomad EAS exome

AF:

0.239

Gnomad FIN exome

AF:

0.451

Gnomad NFE exome

AF:

0.552

Gnomad OTH exome

AF:

0.491

GnomAD4 exome

AF:

0.530

AC:

771611

AN:

1455804

Hom.:

208650

Cov.:

AF XY:

0.531

AC XY:

384048

AN XY:

723786

show subpopulations

African (AFR)

AF:

0.409

AC:

13652

AN:

33386

American (AMR)

AF:

0.325

AC:

14463

AN:

44484

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

15337

AN:

26066

East Asian (EAS)

AF:

0.261

AC:

10360

AN:

39676

South Asian (SAS)

AF:

0.473

AC:

40470

AN:

85520

European-Finnish (FIN)

AF:

0.456

AC:

23746

AN:

52018

Middle Eastern (MID)

AF:

0.571

AC:

2450

AN:

4292

European-Non Finnish (NFE)

AF:

0.559

AC:

620368

AN:

1110246

Other (OTH)

AF:

0.512

AC:

30765

AN:

60116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

18913

37826

56739

75652

94565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17202

34404

51606

68808

86010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.486

AC:

72862

AN:

149990

Hom.:

18337

Cov.:

AF XY:

0.481

AC XY:

35166

AN XY:

73064

show subpopulations

African (AFR)

AF:

0.411

AC:

16715

AN:

40650

American (AMR)

AF:

0.408

AC:

6143

AN:

15060

Ashkenazi Jewish (ASJ)

AF:

0.587

AC:

2032

AN:

3460

East Asian (EAS)

AF:

0.252

AC:

1282

AN:

5088

South Asian (SAS)

AF:

0.458

AC:

2164

AN:

4730

European-Finnish (FIN)

AF:

0.475

AC:

4763

AN:

10026

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.560

AC:

37893

AN:

67688

Other (OTH)

AF:

0.500

AC:

1043

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1787

3574

5361

7148

8935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.529

Hom.:

28700

Bravo

AF:

0.473

Asia WGS

AF:

0.380

AC:

1324

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital microvillous atrophy

Benign:4

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Oct 10, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

7.6

(source)

DANN

Benign

0.75

PhyloP100

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over