Variant rs12489851 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015175.3(NBEAL2):c.4704C>T(p.Asn1568=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0285 in 1,613,894 control chromosomes in the GnomAD database, including 2,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 226 hom., cov: 33)

Exomes 𝑓: 0.028 ( 1955 hom. )

Consequence

NBEAL2
NM_015175.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.83

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 3-47001748-C-T is Benign according to our data. Variant chr3-47001748-C-T is described in ClinVar as [Benign]. Clinvar id is 260580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.83 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBEAL2	NM_015175.3 linkuse as main transcript	c.4704C>T	p.Asn1568=	synonymous_variant	30/54	ENST00000450053.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBEAL2	ENST00000450053.8 linkuse as main transcript	c.4704C>T	p.Asn1568=	synonymous_variant	30/54	2	NM_015175.3	P2	Q6ZNJ1-1
NBEAL2	ENST00000416683.5 linkuse as main transcript	c.2568C>T	p.Asn856=	synonymous_variant	16/40	1
NBEAL2	ENST00000651747.1 linkuse as main transcript	c.4602C>T	p.Asn1534=	synonymous_variant	29/53			A2
NBEAL2	ENST00000475689.1 linkuse as main transcript	n.549C>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.0304

AC:

4621

AN:

152188

Hom.:

226

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00765

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.0617

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.0494

Gnomad FIN

AF:

0.0145

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0277

GnomAD3 exomes

AF:

0.0612

AC:

15251

AN:

249078

Hom.:

1263

AF XY:

0.0538

AC XY:

7271

AN XY:

135192

show subpopulations

Gnomad AFR exome

AF:

0.00808

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.0616

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.0440

Gnomad FIN exome

AF:

0.0172

Gnomad NFE exome

AF:

0.0191

Gnomad OTH exome

AF:

0.0459

GnomAD4 exome

AF:

0.0283

AC:

41363

AN:

1461588

Hom.:

1955

Cov.:

AF XY:

0.0280

AC XY:

20342

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.00621

Gnomad4 AMR exome

AF:

0.214

Gnomad4 ASJ exome

AF:

0.0618

Gnomad4 EAS exome

AF:

0.143

Gnomad4 SAS exome

AF:

0.0421

Gnomad4 FIN exome

AF:

0.0183

Gnomad4 NFE exome

AF:

0.0159

Gnomad4 OTH exome

AF:

0.0296

GnomAD4 genome

AF:

0.0304

AC:

4629

AN:

152306

Hom.:

226

Cov.:

AF XY:

0.0331

AC XY:

2465

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00768

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.0617

Gnomad4 EAS

AF:

0.131

Gnomad4 SAS

AF:

0.0495

Gnomad4 FIN

AF:

0.0145

Gnomad4 NFE

AF:

0.0171

Gnomad4 OTH

AF:

0.0279

Alfa

AF:

0.0292

Hom.:

141

Bravo

AF:

0.0397

Asia WGS

AF:

0.0580

AC:

201

AN:

3478

EpiCase

AF:

0.0207

EpiControl

AF:

0.0190

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Gray platelet syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

-0.68

CADD

Benign

1.0

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over