rs3816531

Variant names:

• chr3-47006072-T-C
• rs3816531
• NM_015175.3:c.6919+9T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015175.3(NBEAL2):​c.6919+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 1,613,270 control chromosomes in the GnomAD database, including 2,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (357 hom., cov: 33)
  • Exomes 𝑓: 0.030 (2081 hom.)
• Consequence: NBEAL2 NM_015175.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.31
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 3-47006072-T-C is Benign according to our data. Variant chr3-47006072-T-C is described in ClinVar as Benign. ClinVar VariationId is 260591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.124 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.6919+9T>C		intron	N/A	NP_055990.1	Q6ZNJ1-1
	NBEAL2	NM_001365116.2		c.6817+9T>C		intron	N/A	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.6919+9T>C		intron	N/A	ENSP00000415034.2	Q6ZNJ1-1
	NBEAL2	ENST00000416683.5	TSL:1	c.4780+9T>C		intron	N/A	ENSP00000410405.1	H0Y764
	NBEAL2	ENST00000443829.5	TSL:1	c.2023+9T>C		intron	N/A	ENSP00000414560.1	H7C3Y7

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7612 AN: 152150 Hom.: 353 Cov.: 33

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0506

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.0435

GnomAD2 exomes AF: 0.0663 AC: 16481 AN: 248612 AF XY: 0.0575

Gnomad AFR exome AF: 0.0786

Gnomad AMR exome AF: 0.231

Gnomad ASJ exome AF: 0.0653

Gnomad EAS exome AF: 0.137

Gnomad FIN exome AF: 0.0170

Gnomad NFE exome AF: 0.0194

Gnomad OTH exome AF: 0.0471

GnomAD4 exome AF: 0.0304 AC: 44346 AN: 1461002 Hom.: 2081 Cov.: 34 AF XY: 0.0297 AC XY: 21583 AN XY: 726742

African (AFR) AF: 0.0767 AC: 2567 AN: 33468

American (AMR) AF: 0.217 AC: 9700 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0661 AC: 1727 AN: 26126

East Asian (EAS) AF: 0.143 AC: 5695 AN: 39690

South Asian (SAS) AF: 0.0421 AC: 3632 AN: 86248

European-Finnish (FIN) AF: 0.0182 AC: 968 AN: 53118

Middle Eastern (MID) AF: 0.0428 AC: 247 AN: 5768

European-Non Finnish (NFE) AF: 0.0160 AC: 17754 AN: 1111524

Other (OTH) AF: 0.0341 AC: 2056 AN: 60350

GnomAD4 genome AF: 0.0501 AC: 7633 AN: 152268 Hom.: 357 Cov.: 33 AF XY: 0.0519 AC XY: 3861 AN XY: 74452

African (AFR) AF: 0.0761 AC: 3164 AN: 41552

American (AMR) AF: 0.123 AC: 1876 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0649 AC: 225 AN: 3468

East Asian (EAS) AF: 0.132 AC: 683 AN: 5184

South Asian (SAS) AF: 0.0506 AC: 244 AN: 4822

European-Finnish (FIN) AF: 0.0145 AC: 154 AN: 10608

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0173 AC: 1178 AN: 68010

Other (OTH) AF: 0.0435 AC: 92 AN: 2116

Alfa AF: 0.0382 Hom.: 97

Bravo AF: 0.0622

Asia WGS AF: 0.0650 AC: 225 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.13
DANN	Benign	0.73
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3816531; hg19: chr3-47047562; COSMIC: COSV52757124; COSMIC: COSV52757124;