Variant 3-46995266-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_015175.3(NBEAL2):c.1531C>T(p.Arg511Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000272 in 1,559,732 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R511G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00022 ( 2 hom. )

Consequence

NBEAL2
NM_015175.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021525621).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000716 (109/152202) while in subpopulation AFR AF= 0.00089 (37/41550). AF 95% confidence interval is 0.000664. There are 0 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBEAL2	NM_015175.3 linkuse as main transcript	c.1531C>T	p.Arg511Cys	missense_variant	13/54	ENST00000450053.8	NP_055990.1	Q6ZNJ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBEAL2	ENST00000450053.8 linkuse as main transcript	c.1531C>T	p.Arg511Cys	missense_variant	13/54	2	NM_015175.3	ENSP00000415034.2		Q6ZNJ1-1
NBEAL2	ENST00000651747.1 linkuse as main transcript	c.1429C>T	p.Arg477Cys	missense_variant	12/53			ENSP00000499216.1		A0A494C1V1

Frequencies

GnomAD3 genomes

AF:

0.000717

AC:

109

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00576

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000671

AC:

111

AN:

165452

Hom.:

AF XY:

0.000583

AC XY:

AN XY:

89234

show subpopulations

Gnomad AFR exome

AF:

0.000815

Gnomad AMR exome

AF:

0.0000387

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00607

Gnomad NFE exome

AF:

0.0000602

Gnomad OTH exome

AF:

0.000869

GnomAD4 exome

AF:

0.000225

AC:

316

AN:

1407530

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

143

AN XY:

695326

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.0000543

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00506

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.000154

GnomAD4 genome

AF:

0.000716

AC:

109

AN:

152202

Hom.:

Cov.:

AF XY:

0.000954

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00576

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000332

Hom.:

1216

ExAC

AF:

0.000335

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

Eigen

Benign

0.015

Eigen_PC

Benign

-0.011

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.76

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.9

REVEL

Benign

0.088

Sift

Benign

0.045

Polyphen

0.98

Vest4

0.32

MVP

0.082

MPC

0.50

ClinPred

0.017

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.088

gMVP

0.32

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over