3-47002132-G-A

Variant names:

• chr3-47002132-G-A
• rs2305635
• NM_015175.3:c.4995G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_015175.3(NBEAL2):​c.4995G>A​(p.Val1665Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,550,500 control chromosomes in the GnomAD database, including 119,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9563 hom., cov: 34)
  • Exomes 𝑓: 0.39 (109867 hom.)
• Consequence: NBEAL2 NM_015175.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.438
• Publications: 20 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.052).
• BP6: Variant 3-47002132-G-A is Benign according to our data. Variant chr3-47002132-G-A is described in ClinVar as Benign. ClinVar VariationId is 260583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.438 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015175.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEAL2	NM_015175.3	MANE Select	c.4995G>A	p.Val1665Val	synonymous	Exon 31 of 54	NP_055990.1	Q6ZNJ1-1
	NBEAL2	NM_001365116.2		c.4893G>A	p.Val1631Val	synonymous	Exon 30 of 53	NP_001352045.1	A0A494C1V1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEAL2	ENST00000450053.8	TSL:2 MANE Select	c.4995G>A	p.Val1665Val	synonymous	Exon 31 of 54	ENSP00000415034.2	Q6ZNJ1-1
	NBEAL2	ENST00000416683.5	TSL:1	c.2856G>A	p.Val952Val	synonymous	Exon 17 of 40	ENSP00000410405.1	H0Y764
	NBEAL2	ENST00000443829.5	TSL:1	c.99G>A	p.Val33Val	synonymous	Exon 1 of 23	ENSP00000414560.1	H7C3Y7

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52658 AN: 152012 Hom.: 9565 Cov.: 34

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.373

GnomAD2 exomes AF: 0.364 AC: 55393 AN: 152366 AF XY: 0.374

Gnomad AFR exome AF: 0.227

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.405

Gnomad EAS exome AF: 0.318

Gnomad FIN exome AF: 0.367

Gnomad NFE exome AF: 0.410

Gnomad OTH exome AF: 0.378

GnomAD4 exome AF: 0.393 AC: 549865 AN: 1398370 Hom.: 109867 Cov.: 71 AF XY: 0.395 AC XY: 272732 AN XY: 689836

African (AFR) AF: 0.237 AC: 7479 AN: 31598

American (AMR) AF: 0.270 AC: 9629 AN: 35708

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 10314 AN: 25158

East Asian (EAS) AF: 0.290 AC: 10346 AN: 35734

South Asian (SAS) AF: 0.407 AC: 32352 AN: 79568

European-Finnish (FIN) AF: 0.375 AC: 17941 AN: 47822

Middle Eastern (MID) AF: 0.469 AC: 2668 AN: 5690

European-Non Finnish (NFE) AF: 0.404 AC: 436444 AN: 1079070

Other (OTH) AF: 0.391 AC: 22692 AN: 58022

GnomAD4 genome AF: 0.346 AC: 52654 AN: 152130 Hom.: 9563 Cov.: 34 AF XY: 0.348 AC XY: 25921 AN XY: 74382

African (AFR) AF: 0.240 AC: 9946 AN: 41522

American (AMR) AF: 0.335 AC: 5131 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1413 AN: 3472

East Asian (EAS) AF: 0.313 AC: 1617 AN: 5170

South Asian (SAS) AF: 0.396 AC: 1906 AN: 4812

European-Finnish (FIN) AF: 0.370 AC: 3916 AN: 10578

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27279 AN: 67966

Other (OTH) AF: 0.372 AC: 783 AN: 2106

Alfa AF: 0.378 Hom.: 7385

Bravo AF: 0.335

Asia WGS AF: 0.311 AC: 1086 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Gray platelet syndrome (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.1
DANN	Benign	0.65
PhyloP100		0.44
PromoterAI		-0.0076	Neutral
Mutation Taster		=293/7	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2305635; hg19: chr3-47043622; COSMIC: COSV52754122; COSMIC: COSV52754122;