chr3-47001748-C-T

Variant names:

• chr3-47001748-C-T
• rs12489851
• NM_015175.3:c.4704C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BA1

The NM_015175.3(NBEAL2):​c.4704C>T​(p.Asn1568Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0285 in 1,613,894 control chromosomes in the GnomAD database, including 2,181 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (226 hom., cov: 33)
  • Exomes 𝑓: 0.028 (1955 hom.)
• Consequence: NBEAL2 NM_015175.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.83
• Publications: 7 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 -17 ACMG points.

• BP6: Variant 3-47001748-C-T is Benign according to our data. Variant chr3-47001748-C-T is described in ClinVar as Benign. ClinVar VariationId is 260580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.123 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.4704C>T	p.Asn1568Asn	synonymous	Exon 30 of 54	NP_055990.1	Q6ZNJ1-1
	NBEAL2	NM_001365116.2		c.4602C>T	p.Asn1534Asn	synonymous	Exon 29 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.4704C>T	p.Asn1568Asn	synonymous	Exon 30 of 54	ENSP00000415034.2	Q6ZNJ1-1
	NBEAL2	ENST00000416683.5	TSL:1	c.2565C>T	p.Asn855Asn	synonymous	Exon 16 of 40	ENSP00000410405.1	H0Y764
	NBEAL2	ENST00000651747.1		c.4602C>T	p.Asn1534Asn	synonymous	Exon 29 of 53	ENSP00000499216.1	A0A494C1V1

Frequencies

GnomAD3 genomes AF: 0.0304 AC: 4621 AN: 152188 Hom.: 226 Cov.: 33

Gnomad AFR AF: 0.00765

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0494

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0277

GnomAD2 exomes AF: 0.0612 AC: 15251 AN: 249078 AF XY: 0.0538

Gnomad AFR exome AF: 0.00808

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.0616

Gnomad EAS exome AF: 0.137

Gnomad FIN exome AF: 0.0172

Gnomad NFE exome AF: 0.0191

Gnomad OTH exome AF: 0.0459

GnomAD4 exome AF: 0.0283 AC: 41363 AN: 1461588 Hom.: 1955 Cov.: 31 AF XY: 0.0280 AC XY: 20342 AN XY: 727064

African (AFR) AF: 0.00621 AC: 208 AN: 33480

American (AMR) AF: 0.214 AC: 9564 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0618 AC: 1615 AN: 26136

East Asian (EAS) AF: 0.143 AC: 5685 AN: 39700

South Asian (SAS) AF: 0.0421 AC: 3633 AN: 86258

European-Finnish (FIN) AF: 0.0183 AC: 974 AN: 53298

Middle Eastern (MID) AF: 0.0416 AC: 240 AN: 5768

European-Non Finnish (NFE) AF: 0.0159 AC: 17656 AN: 1111862

Other (OTH) AF: 0.0296 AC: 1788 AN: 60368

GnomAD4 genome AF: 0.0304 AC: 4629 AN: 152306 Hom.: 226 Cov.: 33 AF XY: 0.0331 AC XY: 2465 AN XY: 74456

African (AFR) AF: 0.00768 AC: 319 AN: 41556

American (AMR) AF: 0.117 AC: 1783 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0617 AC: 214 AN: 3470

East Asian (EAS) AF: 0.131 AC: 680 AN: 5178

South Asian (SAS) AF: 0.0495 AC: 239 AN: 4832

European-Finnish (FIN) AF: 0.0145 AC: 154 AN: 10614

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0171 AC: 1163 AN: 68038

Other (OTH) AF: 0.0279 AC: 59 AN: 2114

Alfa AF: 0.0287 Hom.: 151

Bravo AF: 0.0397

Asia WGS AF: 0.0580 AC: 201 AN: 3478

EpiCase AF: 0.0207

EpiControl AF: 0.0190

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Gray platelet syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.0
DANN	Benign	0.72
PhyloP100		-4.8
PromoterAI		0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12489851; hg19: chr3-47043238; COSMIC: COSV52755552; COSMIC: COSV52755552;