rs115611407

Variant summary

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

The NM_015175.3(NBEAL2):c.1353G>A(p.Pro451=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 1,567,158 control chromosomes in the GnomAD database, including 1,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 232 hom., cov: 33)

Exomes 𝑓: 0.027 ( 1683 hom. )

Consequence

NBEAL2
NM_015175.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.77

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=-0.83).

BP6

Variant 3-46995088-G-A is Benign according to our data. Variant chr3-46995088-G-A is described in ClinVar as [Benign]. Clinvar id is 260578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.77 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.1353G>A	p.Pro451=	synonymous_variant	13/54	ENST00000450053.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBEAL2	ENST00000450053.8 linkuse as main transcript	c.1353G>A	p.Pro451=	synonymous_variant	13/54	2	NM_015175.3	P2	Q6ZNJ1-1
NBEAL2	ENST00000651747.1 linkuse as main transcript	c.1251G>A	p.Pro417=	synonymous_variant	12/53			A2

Frequencies

GnomAD3 genomes

AF:

0.0311

AC:

4739

AN:

152226

Hom.:

231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.0616

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.0499

Gnomad FIN

AF:

0.0145

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0623

AC:

11672

AN:

187312

Hom.:

959

AF XY:

0.0547

AC XY:

5564

AN XY:

101646

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.221

Gnomad ASJ exome

AF:

0.0624

Gnomad EAS exome

AF:

0.133

Gnomad SAS exome

AF:

0.0432

Gnomad FIN exome

AF:

0.0162

Gnomad NFE exome

AF:

0.0175

Gnomad OTH exome

AF:

0.0489

GnomAD4 exome

AF:

0.0272

AC:

38427

AN:

1414814

Hom.:

1683

Cov.:

AF XY:

0.0270

AC XY:

18863

AN XY:

698542

show subpopulations

Gnomad4 AFR exome

AF:

0.00878

Gnomad4 AMR exome

AF:

0.205

Gnomad4 ASJ exome

AF:

0.0618

Gnomad4 EAS exome

AF:

0.142

Gnomad4 SAS exome

AF:

0.0419

Gnomad4 FIN exome

AF:

0.0182

Gnomad4 NFE exome

AF:

0.0157

Gnomad4 OTH exome

AF:

0.0299

GnomAD4 genome

AF:

0.0312

AC:

4754

AN:

152344

Hom.:

232

Cov.:

AF XY:

0.0339

AC XY:

2527

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0105

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.0616

Gnomad4 EAS

AF:

0.132

Gnomad4 SAS

AF:

0.0499

Gnomad4 FIN

AF:

0.0145

Gnomad4 NFE

AF:

0.0171

Gnomad4 OTH

AF:

0.0288

Alfa

AF:

0.0167

Hom.:

Bravo

AF:

0.0406

Asia WGS

AF:

0.0590

AC:

207

AN:

3478

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 13, 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

-0.83

Cadd

Benign

0.13

Dann

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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