Genetic Variant NBEAL2:c.6560+31G>C (chr3-47005352-G-C) – ACMG Classification: Benign (-20 pts)

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.6560+31G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,597,436 control chromosomes in the GnomAD database, including 261,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23417 hom., cov: 34)

Exomes 𝑓: 0.57 ( 238451 hom. )

Consequence

NBEAL2
NM_015175.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.742

Publications

16 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=-0.86).

BP6

Variant 3-47005352-G-C is Benign according to our data. Variant chr3-47005352-G-C is described in ClinVar as Benign. ClinVar VariationId is 260588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015175.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEAL2	NM_015175.3	MANE Select	c.6560+31G>C		intron	N/A	NP_055990.1	Q6ZNJ1-1
	NBEAL2	NM_001365116.2		c.6458+31G>C		intron	N/A	NP_001352045.1	A0A494C1V1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NBEAL2	ENST00000450053.8	TSL:2 MANE Select	c.6560+31G>C	intron	N/A	ENSP00000415034.2	Q6ZNJ1-1
NBEAL2	ENST00000416683.5	TSL:1	c.4421+31G>C	intron	N/A	ENSP00000410405.1	H0Y764
NBEAL2	ENST00000443829.5	TSL:1	c.1664+31G>C	intron	N/A	ENSP00000414560.1	H7C3Y7

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83860

AN:

151974

Hom.:

23383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.526

Gnomad ASJ

AF:

0.527

Gnomad EAS

AF:

0.555

Gnomad SAS

AF:

0.541

Gnomad FIN

AF:

0.614

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.544

GnomAD2 exomes

AF:

0.555

AC:

123627

AN:

222748

AF XY:

0.555

show subpopulations

Gnomad AFR exome

AF:

0.503

Gnomad AMR exome

AF:

0.514

Gnomad ASJ exome

AF:

0.529

Gnomad EAS exome

AF:

0.545

Gnomad FIN exome

AF:

0.613

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.571

GnomAD4 exome

AF:

0.573

AC:

828677

AN:

1445344

Hom.:

238451

Cov.:

AF XY:

0.572

AC XY:

410238

AN XY:

717684

show subpopulations

African (AFR)

AF:

0.501

AC:

16588

AN:

33122

American (AMR)

AF:

0.513

AC:

21703

AN:

42312

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

13519

AN:

25812

East Asian (EAS)

AF:

0.565

AC:

21947

AN:

38866

South Asian (SAS)

AF:

0.538

AC:

45530

AN:

84624

European-Finnish (FIN)

AF:

0.605

AC:

30576

AN:

50512

Middle Eastern (MID)

AF:

0.471

AC:

2709

AN:

5750

European-Non Finnish (NFE)

AF:

0.582

AC:

642376

AN:

1104568

Other (OTH)

AF:

0.564

AC:

33729

AN:

59778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

20847

41693

62540

83386

104233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17718

35436

53154

70872

88590

<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:

0.552

AC:

83944

AN:

152092

Hom.:

23417

Cov.:

AF XY:

0.549

AC XY:

40844

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.501

AC:

20773

AN:

41490

American (AMR)

AF:

0.526

AC:

8045

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.527

AC:

1831

AN:

3472

East Asian (EAS)

AF:

0.555

AC:

2858

AN:

5146

South Asian (SAS)

AF:

0.541

AC:

2609

AN:

4824

European-Finnish (FIN)

AF:

0.614

AC:

6497

AN:

10578

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.583

AC:

39655

AN:

67962

Other (OTH)

AF:

0.546

AC:

1155

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2016

4033

6049

8066

10082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<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:

0.563

Hom.:

4454

Bravo

AF:

0.543

Asia WGS

AF:

0.607

AC:

2106

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Gray platelet syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.74

(source)

DANN

Benign

0.47

PhyloP100

-0.74

PromoterAI

0.029

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over