chr3-47002632-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015175.3(NBEAL2):c.5302-13A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,608,510 control chromosomes in the GnomAD database, including 790,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 69431 hom., cov: 34)

Exomes 𝑓: 0.99 ( 720942 hom. )

Consequence

NBEAL2
NM_015175.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.19

Publications

8 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-47002632-A-T is Benign according to our data. Variant chr3-47002632-A-T is described in ClinVar as Benign. ClinVar VariationId is 260584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEAL2	NM_015175.3 link	c.5302-13A>T		intron_variant	Intron 32 of 53	ENST00000450053.8	NP_055990.1	Q6ZNJ1-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NBEAL2	ENST00000450053.8 link	c.5302-13A>T	intron_variant	Intron 32 of 53	2	NM_015175.3	ENSP00000415034.2	Q6ZNJ1-1
NBEAL2	ENST00000416683.5 link	c.3163-13A>T	intron_variant	Intron 18 of 39	1		ENSP00000410405.1	H0Y764
NBEAL2	ENST00000443829.5 link	c.406-13A>T	intron_variant	Intron 2 of 22	1		ENSP00000414560.1	H7C3Y7
NBEAL2	ENST00000651747.1 link	c.5200-13A>T	intron_variant	Intron 31 of 52			ENSP00000499216.1	A0A494C1V1

Frequencies

GnomAD3 genomes

AF:

0.952

AC:

144839

AN:

152172

Hom.:

69385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.834

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.982

Gnomad ASJ

AF:

0.994

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.961

GnomAD2 exomes

AF:

0.989

AC:

232179

AN:

234872

AF XY:

0.991

show subpopulations

Gnomad AFR exome

AF:

0.833

Gnomad AMR exome

AF:

0.993

Gnomad ASJ exome

AF:

0.994

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.993

GnomAD4 exome

AF:

0.995

AC:

1448547

AN:

1456220

Hom.:

720942

Cov.:

AF XY:

0.995

AC XY:

720669

AN XY:

724048

show subpopulations

African (AFR)

AF:

0.834

AC:

27874

AN:

33426

American (AMR)

AF:

0.991

AC:

43674

AN:

44076

Ashkenazi Jewish (ASJ)

AF:

0.993

AC:

25796

AN:

25972

East Asian (EAS)

AF:

1.00

AC:

39600

AN:

39600

South Asian (SAS)

AF:

1.00

AC:

85562

AN:

85578

European-Finnish (FIN)

AF:

1.00

AC:

51161

AN:

51164

Middle Eastern (MID)

AF:

0.986

AC:

5683

AN:

5762

European-Non Finnish (NFE)

AF:

0.999

AC:

1109684

AN:

1110456

Other (OTH)

AF:

0.989

AC:

59513

AN:

60186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

434

869

1303

1738

2172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21642

43284

64926

86568

108210

<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:

0.952

AC:

144945

AN:

152290

Hom.:

69431

Cov.:

AF XY:

0.954

AC XY:

71019

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.834

AC:

34643

AN:

41536

American (AMR)

AF:

0.982

AC:

15040

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.994

AC:

3450

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5166

AN:

5166

South Asian (SAS)

AF:

1.00

AC:

4830

AN:

4832

European-Finnish (FIN)

AF:

1.00

AC:

10628

AN:

10628

Middle Eastern (MID)

AF:

0.986

AC:

290

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67954

AN:

68026

Other (OTH)

AF:

0.961

AC:

2032

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

317

634

952

1269

1586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<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:

0.978

Hom.:

13375

Bravo

AF:

0.945

Asia WGS

AF:

0.993

AC:

3455

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

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

Jun 09, 2021

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

-0.82

CADD

Benign

0.10

(source)

DANN

Benign

0.45

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over