Variant rs73075647 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.4783-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,605,488 control chromosomes in the GnomAD database, including 28,094 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 0.17 ( 2296 hom., cov: 33)

Exomes 𝑓: 0.18 ( 25798 hom. )

Consequence

NBEAL2
NM_015175.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.847

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:

NBEAL2 (HGNC:):

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 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-47001896-C-T is Benign according to our data. Variant chr3-47001896-C-T is described in ClinVar as [Benign]. Clinvar id is 260581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBEAL2	NM_015175.3 linkuse as main transcript	c.4783-24C>T		intron_variant		ENST00000450053.8	NP_055990.1	Q6ZNJ1-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
NBEAL2	ENST00000450053.8 linkuse as main transcript	c.4783-24C>T	intron_variant	2	NM_015175.3	ENSP00000415034.2	Q6ZNJ1-1
NBEAL2	ENST00000416683.5 linkuse as main transcript	c.2644-24C>T	intron_variant	1		ENSP00000410405.1	H0Y764
NBEAL2	ENST00000651747.1 linkuse as main transcript	c.4681-24C>T	intron_variant			ENSP00000499216.1	A0A494C1V1
NBEAL2	ENST00000475689.1 linkuse as main transcript	n.628-24C>T	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25504

AN:

152034

Hom.:

2293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.261

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0972

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.185

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.173

GnomAD3 exomes

AF:

0.152

AC:

37637

AN:

246880

Hom.:

3472

AF XY:

0.155

AC XY:

20750

AN XY:

134136

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.0860

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.000334

Gnomad SAS exome

AF:

0.0967

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.166

GnomAD4 exome

AF:

0.183

AC:

265437

AN:

1453334

Hom.:

25798

Cov.:

AF XY:

0.181

AC XY:

130586

AN XY:

721212

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.0904

Gnomad4 ASJ exome

AF:

0.178

Gnomad4 EAS exome

AF:

0.000304

Gnomad4 SAS exome

AF:

0.0970

Gnomad4 FIN exome

AF:

0.174

Gnomad4 NFE exome

AF:

0.202

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.168

AC:

25502

AN:

152154

Hom.:

2296

Cov.:

AF XY:

0.163

AC XY:

12092

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.180

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0977

Gnomad4 FIN

AF:

0.167

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.171

Alfa

AF:

0.190

Hom.:

495

Bravo

AF:

0.162

Asia WGS

AF:

0.0450

AC:

159

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 20, 2021	- -
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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.5

DANN

Benign

0.65

BranchPoint Hunter

0.0

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