chr3-47002132-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015175.3(NBEAL2):c.4995G>A(p.Val1665Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,550,500 control chromosomes in the GnomAD database, including 119,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9563 hom., cov: 34)

Exomes 𝑓: 0.39 ( 109867 hom. )

Consequence

NBEAL2
NM_015175.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.438

Publications

20 publications found

Variant links:

Genes affected

NBEAL2 (HGNC:31928): (neurobeachin like 2) The protein encoded by this gene contains a beige and Chediak-Higashi (BEACH) domain and multiple WD40 domains, and may play a role in megakaryocyte alpha-granule biogenesis. Mutations in this gene are a cause of gray platelet syndrome. [provided by RefSeq, Dec 2011]

NBEAL2 Gene-Disease associations (from GenCC):

gray platelet syndrome
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

NBEAL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.052).

BP6

Variant 3-47002132-G-A is Benign according to our data. Variant chr3-47002132-G-A is described in ClinVar as Benign. ClinVar VariationId is 260583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.438 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEAL2	NM_015175.3 link	c.4995G>A	p.Val1665Val	synonymous_variant	Exon 31 of 54	ENST00000450053.8	NP_055990.1	Q6ZNJ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBEAL2	ENST00000450053.8 link	c.4995G>A	p.Val1665Val	synonymous_variant	Exon 31 of 54	2	NM_015175.3	ENSP00000415034.2		Q6ZNJ1-1

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52658

AN:

152012

Hom.:

9565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.240

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.314

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.401

Gnomad OTH

AF:

0.373

GnomAD2 exomes

AF:

0.364

AC:

55393

AN:

152366

AF XY:

0.374

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.367

Gnomad NFE exome

AF:

0.410

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.393

AC:

549865

AN:

1398370

Hom.:

109867

Cov.:

AF XY:

0.395

AC XY:

272732

AN XY:

689836

show subpopulations

African (AFR)

AF:

0.237

AC:

7479

AN:

31598

American (AMR)

AF:

0.270

AC:

9629

AN:

35708

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

10314

AN:

25158

East Asian (EAS)

AF:

0.290

AC:

10346

AN:

35734

South Asian (SAS)

AF:

0.407

AC:

32352

AN:

79568

European-Finnish (FIN)

AF:

0.375

AC:

17941

AN:

47822

Middle Eastern (MID)

AF:

0.469

AC:

2668

AN:

5690

European-Non Finnish (NFE)

AF:

0.404

AC:

436444

AN:

1079070

Other (OTH)

AF:

0.391

AC:

22692

AN:

58022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

20308

40617

60925

81234

101542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13632

27264

40896

54528

68160

<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:

0.346

AC:

52654

AN:

152130

Hom.:

9563

Cov.:

AF XY:

0.348

AC XY:

25921

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.240

AC:

9946

AN:

41522

American (AMR)

AF:

0.335

AC:

5131

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

1413

AN:

3472

East Asian (EAS)

AF:

0.313

AC:

1617

AN:

5170

South Asian (SAS)

AF:

0.396

AC:

1906

AN:

4812

European-Finnish (FIN)

AF:

0.370

AC:

3916

AN:

10578

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.401

AC:

27279

AN:

67966

Other (OTH)

AF:

0.372

AC:

783

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1667

3334

5000

6667

8334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<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:

0.378

Hom.:

7385

Bravo

AF:

0.335

Asia WGS

AF:

0.311

AC:

1086

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Gray platelet syndrome

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.1

(source)

DANN

Benign

0.65

PhyloP100

0.44

PromoterAI

-0.0076

Neutral

(source)

Mutation Taster

=293/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over