rs3826579

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080467.3(MYO5B):c.3591C>T(p.Tyr1197Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.22 in 1,613,140 control chromosomes in the GnomAD database, including 41,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4531 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36902 hom. )

Consequence

MYO5B
NM_001080467.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.95

Publications

18 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 18-49872179-G-A is Benign according to our data. Variant chr18-49872179-G-A is described in ClinVar as Benign. ClinVar VariationId is 327025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3 link	c.3591C>T	p.Tyr1197Tyr	synonymous_variant	Exon 27 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.3591C>T	p.Tyr1197Tyr	synonymous_variant	Exon 27 of 40	1	NM_001080467.3	ENSP00000285039.6		Q9ULV0-1

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36500

AN:

151886

Hom.:

4523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.225

GnomAD2 exomes

AF:

0.255

AC:

63750

AN:

249532

AF XY:

0.256

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.226

Gnomad EAS exome

AF:

0.434

Gnomad FIN exome

AF:

0.258

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.218

AC:

318281

AN:

1461136

Hom.:

36902

Cov.:

AF XY:

0.221

AC XY:

160636

AN XY:

726914

show subpopulations

African (AFR)

AF:

0.268

AC:

8955

AN:

33462

American (AMR)

AF:

0.262

AC:

11716

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

5858

AN:

26130

East Asian (EAS)

AF:

0.384

AC:

15237

AN:

39698

South Asian (SAS)

AF:

0.339

AC:

29224

AN:

86234

European-Finnish (FIN)

AF:

0.258

AC:

13754

AN:

53406

Middle Eastern (MID)

AF:

0.236

AC:

1354

AN:

5744

European-Non Finnish (NFE)

AF:

0.196

AC:

218243

AN:

1111382

Other (OTH)

AF:

0.231

AC:

13940

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

13078

26156

39233

52311

65389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7820

15640

23460

31280

39100

<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:

0.240

AC:

36546

AN:

152004

Hom.:

4531

Cov.:

AF XY:

0.246

AC XY:

18267

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.273

AC:

11301

AN:

41444

American (AMR)

AF:

0.247

AC:

3768

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

745

AN:

3466

East Asian (EAS)

AF:

0.419

AC:

2160

AN:

5152

South Asian (SAS)

AF:

0.341

AC:

1640

AN:

4806

European-Finnish (FIN)

AF:

0.258

AC:

2730

AN:

10564

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.198

AC:

13482

AN:

67982

Other (OTH)

AF:

0.228

AC:

479

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1390

2779

4169

5558

6948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.216

Hom.:

10361

Bravo

AF:

0.240

Asia WGS

AF:

0.362

AC:

1258

AN:

3478

EpiCase

AF:

0.201

EpiControl

AF:

0.201

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

Congenital microvillous atrophy

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

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

-0.49

CADD

Benign

5.8

(source)

DANN

Benign

0.86

PhyloP100

3.9

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