Genetic Variant NM_001395058.1:c.7431T>C (chr17-75620008-T-C) – 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.7431T>C(p.Asn2477Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 701,504 control chromosomes in the GnomAD database, including 42,581 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 0.33 ( 8655 hom., cov: 34)

Exomes 𝑓: 0.34 ( 33926 hom. )

Consequence

MYO15B
NM_001395058.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.706

Publications

19 publications found

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:

Genome browser will be placed here

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=-0.88).

BP7

Synonymous conserved (PhyloP=-0.706 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO15B	NM_001395058.1 link	c.7431T>C	p.Asn2477Asn	synonymous_variant	Exon 47 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.7431T>C	p.Asn2477Asn	synonymous_variant	Exon 47 of 64		NM_001395058.1	ENSP00000495242.3		A0A2R8YFM0

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50520

AN:

152048

Hom.:

8657

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.294

Gnomad ASJ

AF:

0.467

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.357

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.372

Gnomad OTH

AF:

0.348

GnomAD2 exomes

AF:

0.322

AC:

44268

AN:

137508

AF XY:

0.323

show subpopulations

Gnomad AFR exome

AF:

0.288

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.365

Gnomad NFE exome

AF:

0.377

Gnomad OTH exome

AF:

0.364

GnomAD4 exome

AF:

0.344

AC:

188971

AN:

549338

Hom.:

33926

Cov.:

AF XY:

0.341

AC XY:

101527

AN XY:

297356

show subpopulations

African (AFR)

AF:

0.300

AC:

4743

AN:

15796

American (AMR)

AF:

0.263

AC:

9110

AN:

34598

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

9712

AN:

19904

East Asian (EAS)

AF:

0.156

AC:

5010

AN:

32092

South Asian (SAS)

AF:

0.266

AC:

16668

AN:

62562

European-Finnish (FIN)

AF:

0.368

AC:

12316

AN:

33512

Middle Eastern (MID)

AF:

0.434

AC:

1763

AN:

4066

European-Non Finnish (NFE)

AF:

0.375

AC:

118687

AN:

316264

Other (OTH)

AF:

0.359

AC:

10962

AN:

30544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

8212

16424

24636

32848

41060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.332

AC:

50527

AN:

152166

Hom.:

8655

Cov.:

AF XY:

0.328

AC XY:

24372

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.295

AC:

12265

AN:

41534

American (AMR)

AF:

0.294

AC:

4498

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.467

AC:

1623

AN:

3472

East Asian (EAS)

AF:

0.160

AC:

827

AN:

5168

South Asian (SAS)

AF:

0.243

AC:

1173

AN:

4828

European-Finnish (FIN)

AF:

0.357

AC:

3779

AN:

10572

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.372

AC:

25262

AN:

67972

Other (OTH)

AF:

0.345

AC:

730

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1807

3614

5421

7228

9035

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

504

1008

1512

2016

2520

<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:

0.352

Hom.:

9783

Bravo

AF:

0.329

Asia WGS

AF:

0.204

AC:

713

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

0.22

(source)

DANN

Benign

0.53

PhyloP100

-0.71

PromoterAI

0.021

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