Variant rs13066214 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015175.3(NBEAL2):c.1033-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,582,038 control chromosomes in the GnomAD database, including 249,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.49 ( 19432 hom., cov: 32)

Exomes 𝑓: 0.56 ( 230390 hom. )

Consequence

NBEAL2
NM_015175.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.05

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 -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-46992447-C-T is Benign according to our data. Variant chr3-46992447-C-T is described in ClinVar as [Benign]. Clinvar id is 260575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 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.1033-28C>T		intron_variant		ENST00000450053.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBEAL2	ENST00000450053.8 linkuse as main transcript	c.1033-28C>T		intron_variant		2	NM_015175.3	P2	Q6ZNJ1-1
NBEAL2	ENST00000651747.1 linkuse as main transcript	c.1011+501C>T		intron_variant				A2

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

73835

AN:

151922

Hom.:

19417

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.490

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.556

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

GnomAD3 exomes

AF:

0.539

AC:

113991

AN:

211412

Hom.:

31260

AF XY:

0.542

AC XY:

62071

AN XY:

114500

show subpopulations

Gnomad AFR exome

AF:

0.277

Gnomad AMR exome

AF:

0.501

Gnomad ASJ exome

AF:

0.522

Gnomad EAS exome

AF:

0.545

Gnomad SAS exome

AF:

0.535

Gnomad FIN exome

AF:

0.615

Gnomad NFE exome

AF:

0.570

Gnomad OTH exome

AF:

0.556

GnomAD4 exome

AF:

0.565

AC:

807379

AN:

1429998

Hom.:

230390

Cov.:

AF XY:

0.564

AC XY:

400143

AN XY:

709618

show subpopulations

Gnomad4 AFR exome

AF:

0.276

Gnomad4 AMR exome

AF:

0.499

Gnomad4 ASJ exome

AF:

0.518

Gnomad4 EAS exome

AF:

0.566

Gnomad4 SAS exome

AF:

0.539

Gnomad4 FIN exome

AF:

0.607

Gnomad4 NFE exome

AF:

0.578

Gnomad4 OTH exome

AF:

0.546

GnomAD4 genome

AF:

0.486

AC:

73882

AN:

152040

Hom.:

19432

Cov.:

AF XY:

0.486

AC XY:

36123

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.282

Gnomad4 AMR

AF:

0.490

Gnomad4 ASJ

AF:

0.524

Gnomad4 EAS

AF:

0.556

Gnomad4 SAS

AF:

0.541

Gnomad4 FIN

AF:

0.615

Gnomad4 NFE

AF:

0.579

Gnomad4 OTH

AF:

0.496

Alfa

AF:

0.533

Hom.:

4113

Bravo

AF:

0.467

Asia WGS

AF:

0.594

AC:

2064

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 19, 2021

- -

Gray platelet syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.10

DANN

Benign

0.74

BranchPoint Hunter

1.0

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