dbSNP rs8107108: MYO9B:c.4372+73C>T (chr19-17200499-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004145.4(MYO9B):c.4372+73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 1,519,530 control chromosomes in the GnomAD database, including 4,786 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.090 ( 728 hom., cov: 32)

Exomes 𝑓: 0.074 ( 4058 hom. )

Consequence

MYO9B
NM_004145.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.67

Publications

5 publications found

Variant links:

Genes affected

MYO9B (HGNC:7609): (myosin IXB) This gene encodes a member of the myosin family of actin-based molecular motor heavy chain proteins. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-9 (MYH9). The protein has four IQ motifs located in the neck domain that bind calmodulin, which serves as a light chain. The protein complex has a single-headed structure and exhibits processive movement on actin filaments toward the minus-end. The protein also has rho-GTPase activity. Polymorphisms in this gene are associated with celiac disease and ulcerative colitis susceptibility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

MYO9B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO9B	NM_004145.4 link	c.4372+73C>T		intron_variant	Intron 25 of 39	ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2 link	c.4372+73C>T		intron_variant	Intron 25 of 39		NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1 link	c.4372+73C>T		intron_variant	Intron 25 of 39		NM_004145.4	ENSP00000507803.1

Frequencies

GnomAD3 genomes

AF:

0.0904

AC:

13740

AN:

152072

Hom.:

724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.0573

Gnomad AMR

AF:

0.0658

Gnomad ASJ

AF:

0.0611

Gnomad EAS

AF:

0.000965

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0732

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0791

Gnomad OTH

AF:

0.0840

GnomAD4 exome

AF:

0.0737

AC:

100791

AN:

1367340

Hom.:

4058

Cov.:

AF XY:

0.0717

AC XY:

48273

AN XY:

672846

show subpopulations

African (AFR)

AF:

0.147

AC:

4442

AN:

30244

American (AMR)

AF:

0.0513

AC:

1533

AN:

29902

Ashkenazi Jewish (ASJ)

AF:

0.0617

AC:

1413

AN:

22912

East Asian (EAS)

AF:

0.000112

AC:

AN:

35562

South Asian (SAS)

AF:

0.0181

AC:

1356

AN:

75090

European-Finnish (FIN)

AF:

0.0765

AC:

3687

AN:

48214

Middle Eastern (MID)

AF:

0.0501

AC:

204

AN:

4070

European-Non Finnish (NFE)

AF:

0.0789

AC:

84027

AN:

1064844

Other (OTH)

AF:

0.0730

AC:

4125

AN:

56502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

5165

10331

15496

20662

25827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3168

6336

9504

12672

15840

<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:

0.0904

AC:

13755

AN:

152190

Hom.:

728

Cov.:

AF XY:

0.0875

AC XY:

6513

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.146

AC:

6057

AN:

41520

American (AMR)

AF:

0.0656

AC:

1003

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0611

AC:

212

AN:

3470

East Asian (EAS)

AF:

0.000967

AC:

AN:

5168

South Asian (SAS)

AF:

0.0172

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0732

AC:

776

AN:

10606

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0791

AC:

5375

AN:

67994

Other (OTH)

AF:

0.0822

AC:

174

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

613

1227

1840

2454

3067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.0784

Hom.:

1008

Bravo

AF:

0.0925

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.20

(source)

DANN

Benign

0.41

PhyloP100

-2.7

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

Computational scores

Splicing

Publications

Other links and lift over