3-47004249-C-G

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.6054C>G(p.Pro2018Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,613,396 control chromosomes in the GnomAD database, including 254,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19430 hom., cov: 31)

Exomes 𝑓: 0.56 ( 235522 hom. )

Consequence

NBEAL2
NM_015175.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.120

Publications

27 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=0.046).

BP6

Variant 3-47004249-C-G is Benign according to our data. Variant chr3-47004249-C-G is described in ClinVar as [Benign]. Clinvar id is 260586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEAL2	NM_015175.3 link	c.6054C>G	p.Pro2018Pro	synonymous_variant	Exon 37 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.6054C>G	p.Pro2018Pro	synonymous_variant	Exon 37 of 54	2	NM_015175.3	ENSP00000415034.2		Q6ZNJ1-1

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

73825

AN:

151820

Hom.:

19414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.490

Gnomad ASJ

AF:

0.523

Gnomad EAS

AF:

0.555

Gnomad SAS

AF:

0.541

Gnomad FIN

AF:

0.615

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.494

GnomAD2 exomes

AF:

0.540

AC:

134582

AN:

249084

AF XY:

0.544

show subpopulations

Gnomad AFR exome

AF:

0.281

Gnomad AMR exome

AF:

0.503

Gnomad ASJ exome

AF:

0.523

Gnomad EAS exome

AF:

0.547

Gnomad FIN exome

AF:

0.615

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.560

GnomAD4 exome

AF:

0.565

AC:

825292

AN:

1461458

Hom.:

235522

Cov.:

AF XY:

0.564

AC XY:

410019

AN XY:

727010

show subpopulations

African (AFR)

AF:

0.278

AC:

9296

AN:

33474

American (AMR)

AF:

0.501

AC:

22385

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

13546

AN:

26126

East Asian (EAS)

AF:

0.566

AC:

22459

AN:

39700

South Asian (SAS)

AF:

0.541

AC:

46631

AN:

86258

European-Finnish (FIN)

AF:

0.607

AC:

32324

AN:

53254

Middle Eastern (MID)

AF:

0.460

AC:

2652

AN:

5766

European-Non Finnish (NFE)

AF:

0.578

AC:

642987

AN:

1111806

Other (OTH)

AF:

0.547

AC:

33012

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

23493

46985

70478

93970

117463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.486

AC:

73872

AN:

151938

Hom.:

19430

Cov.:

AF XY:

0.486

AC XY:

36098

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.283

AC:

11731

AN:

41440

American (AMR)

AF:

0.490

AC:

7482

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.523

AC:

1817

AN:

3472

East Asian (EAS)

AF:

0.555

AC:

2852

AN:

5140

South Asian (SAS)

AF:

0.541

AC:

2597

AN:

4802

European-Finnish (FIN)

AF:

0.615

AC:

6503

AN:

10582

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.579

AC:

39333

AN:

67914

Other (OTH)

AF:

0.496

AC:

1046

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1757

3515

5272

7030

8787

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.468

Hom.:

2585

Bravo

AF:

0.468

Asia WGS

AF:

0.593

AC:

2059

AN:

3478

EpiCase

AF:

0.555

EpiControl

AF:

0.559

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Dec 05, 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 13, 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

-0.84

CADD

Benign

3.6

(source)

DANN

Benign

0.48

PhyloP100

-0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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3-47004249-C-G

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