Variant rs749512 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.1198-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,521,638 control chromosomes in the GnomAD database, including 102,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8431 hom., cov: 33)

Exomes 𝑓: 0.37 ( 94100 hom. )

Consequence

NBEAL2
NM_015175.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0960

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=-0.84).

BP6

Variant 3-46994410-C-T is Benign according to our data. Variant chr3-46994410-C-T is described in ClinVar as [Benign]. Clinvar id is 260576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 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.1198-45C>T		intron_variant		ENST00000450053.8	NP_055990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBEAL2	ENST00000450053.8 linkuse as main transcript	c.1198-45C>T		intron_variant		2	NM_015175.3	ENSP00000415034	P2	Q6ZNJ1-1
NBEAL2	ENST00000651747.1 linkuse as main transcript	c.1096-45C>T		intron_variant				ENSP00000499216	A2

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

49287

AN:

152002

Hom.:

8432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.513

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.357

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.350

GnomAD3 exomes

AF:

0.341

AC:

54711

AN:

160286

Hom.:

9857

AF XY:

0.351

AC XY:

29979

AN XY:

85442

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.237

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.316

Gnomad SAS exome

AF:

0.398

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.352

GnomAD4 exome

AF:

0.367

AC:

503224

AN:

1369518

Hom.:

94100

Cov.:

AF XY:

0.370

AC XY:

250650

AN XY:

677884

show subpopulations

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.378

Gnomad4 EAS exome

AF:

0.289

Gnomad4 SAS exome

AF:

0.395

Gnomad4 FIN exome

AF:

0.357

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.366

GnomAD4 genome

AF:

0.324

AC:

49282

AN:

152120

Hom.:

8431

Cov.:

AF XY:

0.327

AC XY:

24309

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.320

Gnomad4 ASJ

AF:

0.378

Gnomad4 EAS

AF:

0.312

Gnomad4 SAS

AF:

0.386

Gnomad4 FIN

AF:

0.357

Gnomad4 NFE

AF:

0.370

Gnomad4 OTH

AF:

0.348

Alfa

AF:

0.362

Hom.:

5371

Bravo

AF:

0.313

Asia WGS

AF:

0.303

AC:

1057

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	Nov 12, 2018	- -
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

-0.84

CADD

Benign

9.1

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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