18-49843388-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001080467.3(MYO5B):c.4464G>A(p.Leu1488Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 1,613,966 control chromosomes in the GnomAD database, including 9,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 950 hom., cov: 33)

Exomes 𝑓: 0.072 ( 8354 hom. )

Consequence

MYO5B
NM_001080467.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.750

Publications

14 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 links:

SNHG22 (HGNC:50285): (small nucleolar RNA host gene 22)

SNHG22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 18-49843388-C-T is Benign according to our data. Variant chr18-49843388-C-T is described in CliVar as Benign. Clinvar id is 327010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49843388-C-T is described in CliVar as Benign. Clinvar id is 327010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49843388-C-T is described in CliVar as Benign. Clinvar id is 327010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49843388-C-T is described in CliVar as Benign. Clinvar id is 327010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49843388-C-T is described in CliVar as Benign. Clinvar id is 327010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49843388-C-T is described in CliVar as Benign. Clinvar id is 327010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49843388-C-T is described in CliVar as Benign. Clinvar id is 327010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.75 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3 link	c.4464G>A	p.Leu1488Leu	synonymous_variant	Exon 34 of 40	ENST00000285039.12	NP_001073936.1	Q9ULV0-1Q7Z7A5
SNHG22	NR_117096.1 link	n.192+2963C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12 link	c.4464G>A	p.Leu1488Leu	synonymous_variant	Exon 34 of 40	1	NM_001080467.3	ENSP00000285039.6		Q9ULV0-1

Frequencies

GnomAD3 genomes

AF:

0.0790

AC:

12019

AN:

152044

Hom.:

941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0528

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0647

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.0477

Gnomad OTH

AF:

0.0876

GnomAD2 exomes

AF:

0.122

AC:

30529

AN:

249252

AF XY:

0.111

show subpopulations

Gnomad AFR exome

AF:

0.0534

Gnomad AMR exome

AF:

0.383

Gnomad ASJ exome

AF:

0.0372

Gnomad EAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.0661

Gnomad NFE exome

AF:

0.0481

Gnomad OTH exome

AF:

0.0949

GnomAD4 exome

AF:

0.0724

AC:

105856

AN:

1461804

Hom.:

8354

Cov.:

AF XY:

0.0722

AC XY:

52529

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.0542

AC:

1816

AN:

33480

American (AMR)

AF:

0.364

AC:

16299

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0364

AC:

952

AN:

26136

East Asian (EAS)

AF:

0.357

AC:

14158

AN:

39698

South Asian (SAS)

AF:

0.115

AC:

9941

AN:

86252

European-Finnish (FIN)

AF:

0.0647

AC:

3456

AN:

53402

Middle Eastern (MID)

AF:

0.0820

AC:

473

AN:

5768

European-Non Finnish (NFE)

AF:

0.0487

AC:

54121

AN:

1111962

Other (OTH)

AF:

0.0768

AC:

4640

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

5530

11060

16589

22119

27649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2410

4820

7230

9640

12050

<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:

0.0792

AC:

12049

AN:

152162

Hom.:

950

Cov.:

AF XY:

0.0840

AC XY:

6250

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0528

AC:

2191

AN:

41530

American (AMR)

AF:

0.229

AC:

3499

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0383

AC:

133

AN:

3472

East Asian (EAS)

AF:

0.292

AC:

1505

AN:

5152

South Asian (SAS)

AF:

0.122

AC:

588

AN:

4822

European-Finnish (FIN)

AF:

0.0647

AC:

685

AN:

10590

Middle Eastern (MID)

AF:

0.0582

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0477

AC:

3241

AN:

68002

Other (OTH)

AF:

0.0882

AC:

186

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

522

1044

1565

2087

2609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0651

Hom.:

1091

Bravo

AF:

0.0945

Asia WGS

AF:

0.187

AC:

648

AN:

3478

EpiCase

AF:

0.0488

EpiControl

AF:

0.0480

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital microvillous atrophy

Benign:1

Jan 12, 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

-0.55

CADD

Benign

9.6

(source)

DANN

Benign

0.59

PhyloP100

0.75

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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