Variant rs3816531 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.6919+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 1,613,270 control chromosomes in the GnomAD database, including 2,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 357 hom., cov: 33)

Exomes 𝑓: 0.030 ( 2081 hom. )

Consequence

NBEAL2
NM_015175.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.31

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

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 3-47006072-T-C is Benign according to our data. Variant chr3-47006072-T-C is described in ClinVar as [Benign]. Clinvar id is 260591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBEAL2	NM_015175.3 link	c.6919+9T>C		intron_variant		ENST00000450053.8	NP_055990.1	Q6ZNJ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBEAL2	ENST00000450053.8 link	c.6919+9T>C		intron_variant		2	NM_015175.3	ENSP00000415034.2		Q6ZNJ1-1

Frequencies

GnomAD3 genomes

AF:

0.0500

AC:

7612

AN:

152150

Hom.:

353

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0760

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.0649

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.0506

Gnomad FIN

AF:

0.0145

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0173

Gnomad OTH

AF:

0.0435

GnomAD3 exomes

AF:

0.0663

AC:

16481

AN:

248612

Hom.:

1329

AF XY:

0.0575

AC XY:

7762

AN XY:

134962

show subpopulations

Gnomad AFR exome

AF:

0.0786

Gnomad AMR exome

AF:

0.231

Gnomad ASJ exome

AF:

0.0653

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.0440

Gnomad FIN exome

AF:

0.0170

Gnomad NFE exome

AF:

0.0194

Gnomad OTH exome

AF:

0.0471

GnomAD4 exome

AF:

0.0304

AC:

44346

AN:

1461002

Hom.:

2081

Cov.:

AF XY:

0.0297

AC XY:

21583

AN XY:

726742

show subpopulations

Gnomad4 AFR exome

AF:

0.0767

Gnomad4 AMR exome

AF:

0.217

Gnomad4 ASJ exome

AF:

0.0661

Gnomad4 EAS exome

AF:

0.143

Gnomad4 SAS exome

AF:

0.0421

Gnomad4 FIN exome

AF:

0.0182

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.0341

GnomAD4 genome

AF:

0.0501

AC:

7633

AN:

152268

Hom.:

357

Cov.:

AF XY:

0.0519

AC XY:

3861

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0761

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.0649

Gnomad4 EAS

AF:

0.132

Gnomad4 SAS

AF:

0.0506

Gnomad4 FIN

AF:

0.0145

Gnomad4 NFE

AF:

0.0173

Gnomad4 OTH

AF:

0.0435

Alfa

AF:

0.0394

Hom.:

Bravo

AF:

0.0622

Asia WGS

AF:

0.0650

AC:

225

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 04, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

-0.69

CADD

Benign

0.13

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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