dbSNP rs73075647: NBEAL2:c.4783-24C>T (chr3-47001896-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

gray platelet syndrome
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

NBEAL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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 rank	MANE	Protein	UniProt
NBEAL2	NM_015175.3 link	c.4783-24C>T		intron_variant	Intron 30 of 53	ENST00000450053.8	NP_055990.1	Q6ZNJ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBEAL2	ENST00000450053.8 link	c.4783-24C>T		intron_variant	Intron 30 of 53	2	NM_015175.3	ENSP00000415034.2		Q6ZNJ1-1

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

GnomAD2 exomes

AF:

0.152

AC:

37637

AN:

246880

AF XY:

0.155

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 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

African (AFR)

AF:

0.148

AC:

4947

AN:

33378

American (AMR)

AF:

0.0904

AC:

4031

AN:

44578

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

4641

AN:

26038

East Asian (EAS)

AF:

0.000304

AC:

AN:

39480

South Asian (SAS)

AF:

0.0970

AC:

8358

AN:

86134

European-Finnish (FIN)

AF:

0.174

AC:

9076

AN:

52118

Middle Eastern (MID)

AF:

0.207

AC:

1191

AN:

5742

European-Non Finnish (NFE)

AF:

0.202

AC:

222891

AN:

1105900

Other (OTH)

AF:

0.172

AC:

10290

AN:

59966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

13820

27641

41461

55282

69102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7542

15084

22626

30168

37710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.168

AC:

25502

AN:

152154

Hom.:

2296

Cov.:

AF XY:

0.163

AC XY:

12092

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.149

AC:

6177

AN:

41522

American (AMR)

AF:

0.126

AC:

1930

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

626

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5180

South Asian (SAS)

AF:

0.0977

AC:

471

AN:

4822

European-Finnish (FIN)

AF:

0.167

AC:

1772

AN:

10598

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.204

AC:

13864

AN:

67952

Other (OTH)

AF:

0.171

AC:

362

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1077

2154

3232

4309

5386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.188

Hom.:

873

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

Jun 20, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.5

(source)

DANN

Benign

0.65

PhyloP100

0.85

BranchPoint Hunter

0.0

PromoterAI

-0.0060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over