Genetic Variant MYO9B:c.5386+67A>G (chr19-17206443-A-G) – 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.5386+67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,565,702 control chromosomes in the GnomAD database, including 106,512 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 0.39 ( 12572 hom., cov: 33)

Exomes 𝑓: 0.35 ( 93940 hom. )

Consequence

MYO9B
NM_004145.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.681

Publications

10 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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO9B	NM_004145.4 link	c.5386+67A>G		intron_variant	Intron 33 of 39	ENST00000682292.1	NP_004136.2	Q13459-1B0I1T6Q8WVD2
MYO9B	NM_001130065.2 link	c.5386+67A>G		intron_variant	Intron 33 of 39		NP_001123537.1	Q8WVD2Q4LE74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1 link	c.5386+67A>G		intron_variant	Intron 33 of 39		NM_004145.4	ENSP00000507803.1		Q13459-1

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

59597

AN:

152022

Hom.:

12561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.438

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.514

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.762

Gnomad SAS

AF:

0.458

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.317

Gnomad OTH

AF:

0.393

GnomAD4 exome

AF:

0.351

AC:

495986

AN:

1413562

Hom.:

93940

AF XY:

0.352

AC XY:

245895

AN XY:

699442

show subpopulations

African (AFR)

AF:

0.447

AC:

14682

AN:

32878

American (AMR)

AF:

0.646

AC:

26605

AN:

41162

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

4993

AN:

24174

East Asian (EAS)

AF:

0.757

AC:

29429

AN:

38876

South Asian (SAS)

AF:

0.434

AC:

34985

AN:

80584

European-Finnish (FIN)

AF:

0.357

AC:

14111

AN:

39578

Middle Eastern (MID)

AF:

0.317

AC:

1717

AN:

5424

European-Non Finnish (NFE)

AF:

0.319

AC:

348258

AN:

1092200

Other (OTH)

AF:

0.361

AC:

21206

AN:

58686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

17742

35485

53227

70970

88712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11786

23572

35358

47144

58930

<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:

0.392

AC:

59625

AN:

152140

Hom.:

12572

Cov.:

AF XY:

0.398

AC XY:

29603

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.438

AC:

18173

AN:

41514

American (AMR)

AF:

0.515

AC:

7870

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

717

AN:

3472

East Asian (EAS)

AF:

0.762

AC:

3927

AN:

5152

South Asian (SAS)

AF:

0.457

AC:

2206

AN:

4828

European-Finnish (FIN)

AF:

0.377

AC:

3990

AN:

10572

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.317

AC:

21558

AN:

67994

Other (OTH)

AF:

0.392

AC:

828

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1838

3676

5515

7353

9191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<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:

0.256

Hom.:

1174

Bravo

AF:

0.410

Asia WGS

AF:

0.559

AC:

1942

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.11

(source)

DANN

Benign

0.50

PhyloP100

-0.68

PromoterAI

0.0011

Neutral

(source)

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