Genetic Variant MYO5B:c.2004-13dupT (chr18-49929610-G-GA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001080467.3(MYO5B):c.2004-13dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00018 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0032 ( 3 hom. )

Consequence

MYO5B
NM_001080467.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.06

Publications

2 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080467.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	NM_001080467.3	MANE Select	c.2004-13dupT		intron	N/A	NP_001073936.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.2004-13_2004-12insT		intron	N/A	ENSP00000285039.6
	MYO5B	ENST00000697219.1		c.1800-13_1800-12insT		intron	N/A	ENSP00000513188.1

Frequencies

GnomAD3 genomes

AF:

0.000181

AC:

AN:

132858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000305

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000224

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00292

AC:

334

AN:

114366

AF XY:

0.00308

show subpopulations

Gnomad AFR exome

AF:

0.00225

Gnomad AMR exome

AF:

0.00144

Gnomad ASJ exome

AF:

0.00273

Gnomad EAS exome

AF:

0.000464

Gnomad FIN exome

AF:

0.00438

Gnomad NFE exome

AF:

0.00389

Gnomad OTH exome

AF:

0.00153

GnomAD4 exome

AF:

0.00325

AC:

3739

AN:

1151044

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

1772

AN XY:

575366

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00324

AC:

AN:

26512

American (AMR)

AF:

0.000937

AC:

AN:

32024

Ashkenazi Jewish (ASJ)

AF:

0.00140

AC:

AN:

22136

East Asian (EAS)

AF:

0.000179

AC:

AN:

33492

South Asian (SAS)

AF:

0.00201

AC:

141

AN:

70048

European-Finnish (FIN)

AF:

0.00238

AC:

AN:

36076

Middle Eastern (MID)

AF:

0.00257

AC:

AN:

3508

European-Non Finnish (NFE)

AF:

0.00366

AC:

3215

AN:

878380

Other (OTH)

AF:

0.00276

AC:

135

AN:

48868

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.301

Heterozygous variant carriers

270

540

811

1081

1351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

288

432

576

720

<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:

0.000181

AC:

AN:

132836

Hom.:

Cov.:

AF XY:

0.000252

AC XY:

AN XY:

63446

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

35464

American (AMR)

AF:

0.000304

AC:

AN:

13142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3244

East Asian (EAS)

AF:

0.00

AC:

AN:

4606

South Asian (SAS)

AF:

0.00

AC:

AN:

4060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6888

Middle Eastern (MID)

AF:

0.00

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.000224

AC:

AN:

62518

Other (OTH)

AF:

0.00

AC:

AN:

1816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00422

Hom.:

142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Mutation Taster

=100/0

polymorphism

(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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18-49929610-GAAAAAAA-GAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over