Genetic Variant MYO15B:p.Thr2714Thr (chr17-75623840-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001395058.1(MYO15B):c.8142G>A(p.Thr2714Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 699,066 control chromosomes in the GnomAD database, including 30,753 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 0.28 ( 6063 hom., cov: 32)

Exomes 𝑓: 0.29 ( 24690 hom. )

Consequence

MYO15B
NM_001395058.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.95

Variant links:

Genes affected

MYO15B (HGNC:14083): (myosin XVB) Predicted to enable ATP binding activity; actin binding activity; and cytoskeletal motor activity. Predicted to be located in brush border; cytoplasm; and cytoskeleton. Predicted to be part of myosin complex. [provided by Alliance of Genome Resources, Apr 2022]

MYO15B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=-1.95 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO15B	NM_001395058.1 link	c.8142G>A	p.Thr2714Thr	synonymous_variant	Exon 54 of 64	ENST00000645453.3	NP_001381987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO15B	ENST00000645453.3 link	c.8142G>A	p.Thr2714Thr	synonymous_variant	Exon 54 of 64		NM_001395058.1	ENSP00000495242.3		A0A2R8YFM0

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

42173

AN:

148254

Hom.:

6065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.313

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.326

Gnomad OTH

AF:

0.300

GnomAD2 exomes

AF:

0.268

AC:

36632

AN:

136718

AF XY:

0.270

show subpopulations

Gnomad AFR exome

AF:

0.222

Gnomad AMR exome

AF:

0.187

Gnomad ASJ exome

AF:

0.399

Gnomad EAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.305

Gnomad NFE exome

AF:

0.328

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.291

AC:

160380

AN:

550696

Hom.:

24690

Cov.:

AF XY:

0.289

AC XY:

86111

AN XY:

298136

show subpopulations

African (AFR)

AF:

0.234

AC:

3694

AN:

15808

American (AMR)

AF:

0.194

AC:

6748

AN:

34704

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

8024

AN:

20026

East Asian (EAS)

AF:

0.130

AC:

4187

AN:

32104

South Asian (SAS)

AF:

0.213

AC:

13396

AN:

62774

European-Finnish (FIN)

AF:

0.306

AC:

10277

AN:

33628

Middle Eastern (MID)

AF:

0.370

AC:

1510

AN:

4076

European-Non Finnish (NFE)

AF:

0.326

AC:

103212

AN:

316962

Other (OTH)

AF:

0.305

AC:

9332

AN:

30614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

7465

14929

22394

29858

37323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.284

AC:

42173

AN:

148370

Hom.:

6063

Cov.:

AF XY:

0.281

AC XY:

20285

AN XY:

72064

show subpopulations

African (AFR)

AF:

0.239

AC:

9591

AN:

40192

American (AMR)

AF:

0.237

AC:

3451

AN:

14536

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

1346

AN:

3450

East Asian (EAS)

AF:

0.164

AC:

803

AN:

4884

South Asian (SAS)

AF:

0.208

AC:

945

AN:

4554

European-Finnish (FIN)

AF:

0.313

AC:

3176

AN:

10142

Middle Eastern (MID)

AF:

0.346

AC:

101

AN:

292

European-Non Finnish (NFE)

AF:

0.326

AC:

21958

AN:

67362

Other (OTH)

AF:

0.298

AC:

614

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1559

3119

4678

6238

7797

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.317

Hom.:

2385

Bravo

AF:

0.274

Asia WGS

AF:

0.170

AC:

594

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.6

(source)

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

chr17-75623840-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over