rs397841722

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1

The NM_001080467.3(MYO5B):c.3163_3165dupCTC(p.Leu1055dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,613,342 control chromosomes in the GnomAD database, including 78,462 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8240 hom., cov: 0)

Exomes 𝑓: 0.30 ( 70222 hom. )

Consequence

MYO5B
NM_001080467.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:6

Conservation

PhyloP100: -0.226

Publications

9 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 -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001080467.3. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 18-49879055-T-TGAG is Benign according to our data. Variant chr18-49879055-T-TGAG is described in ClinVar as Benign. ClinVar VariationId is 327031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3 link	c.3163_3165dupCTC	p.Leu1055dup	conservative_inframe_insertion	Exon 24 of 40	ENST00000285039.12	NP_001073936.1	Q9ULV0-1Q7Z7A5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12 link	c.3163_3165dupCTC	p.Leu1055dup	conservative_inframe_insertion	Exon 24 of 40	1	NM_001080467.3	ENSP00000285039.6		Q9ULV0-1

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

49135

AN:

151762

Hom.:

8235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.363

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.542

Gnomad SAS

AF:

0.501

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.291

GnomAD2 exomes

AF:

0.340

AC:

84825

AN:

249362

AF XY:

0.346

show subpopulations

Gnomad AFR exome

AF:

0.359

Gnomad AMR exome

AF:

0.286

Gnomad ASJ exome

AF:

0.281

Gnomad EAS exome

AF:

0.557

Gnomad FIN exome

AF:

0.364

Gnomad NFE exome

AF:

0.280

Gnomad OTH exome

AF:

0.316

GnomAD4 exome

AF:

0.302

AC:

441199

AN:

1461462

Hom.:

70222

Cov.:

AF XY:

0.308

AC XY:

223571

AN XY:

727058

show subpopulations

African (AFR)

AF:

0.363

AC:

12160

AN:

33470

American (AMR)

AF:

0.286

AC:

12806

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

7271

AN:

26134

East Asian (EAS)

AF:

0.496

AC:

19681

AN:

39696

South Asian (SAS)

AF:

0.493

AC:

42508

AN:

86240

European-Finnish (FIN)

AF:

0.363

AC:

19372

AN:

53398

Middle Eastern (MID)

AF:

0.322

AC:

1857

AN:

5768

European-Non Finnish (NFE)

AF:

0.276

AC:

306608

AN:

1111656

Other (OTH)

AF:

0.314

AC:

18936

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

16855

33711

50566

67422

84277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10490

20980

31470

41960

52450

<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:

0.324

AC:

49182

AN:

151880

Hom.:

8240

Cov.:

AF XY:

0.331

AC XY:

24575

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.363

AC:

15017

AN:

41390

American (AMR)

AF:

0.282

AC:

4311

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

914

AN:

3470

East Asian (EAS)

AF:

0.542

AC:

2791

AN:

5146

South Asian (SAS)

AF:

0.501

AC:

2409

AN:

4810

European-Finnish (FIN)

AF:

0.365

AC:

3843

AN:

10530

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.279

AC:

18951

AN:

67940

Other (OTH)

AF:

0.293

AC:

618

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1689

3378

5066

6755

8444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<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:

0.296

Hom.:

4046

Bravo

AF:

0.315

Asia WGS

AF:

0.484

AC:

1683

AN:

3478

EpiCase

AF:

0.272

EpiControl

AF:

0.270

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital microvillous atrophy

Pathogenic:1Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 05, 2025

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 24014347, 28492530, 25111220) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Diarrhea with Microvillus Atrophy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital microvillous atrophy;C5676981:Cholestasis, progressive familial intrahepatic, 10

Benign:1

Apr 23, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.23

Mutation Taster

=72/28

polymorphism (auto)

(source)

Splicing

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