rs749512

chr3-46994410-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0960

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]

ACMG classification

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	UniProt
NBEAL2	NM_015175.3	c.1198-45C>T		intron_variant		ENST00000450053.8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49287 AN: 152002 Hom.: 8432 Cov.: 33

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

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.: 26 AF XY: 0.370 AC XY: 250650 AN XY: 677884

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.: 33 AF XY: 0.327 AC XY: 24309 AN XY: 74338

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

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

Other links and lift over

dbSNP: rs749512; hg19: chr3-47035900; COSMIC: COSV52756708; COSMIC: COSV52756708;