rs13081418

Variant names:

• chr3-47005868-A-C
• rs13081418
• NM_015175.3:c.6801+21A>C

Variant summary

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

The ENST00000450053.8(NBEAL2):​c.6801+21A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,612,402 control chromosomes in the GnomAD database, including 83,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5692 hom., cov: 33)
  • Exomes 𝑓: 0.32 (78256 hom.)
• Consequence: NBEAL2 ENST00000450053.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.287
• Publications: 11 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=-0.85).
• BP6: Variant 3-47005868-A-C is Benign according to our data. Variant chr3-47005868-A-C is described in ClinVar as Benign. ClinVar VariationId is 260590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000450053.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEAL2	NM_015175.3	MANE Select	c.6801+21A>C		intron	N/A	NP_055990.1
	NBEAL2	NM_001365116.2		c.6699+21A>C		intron	N/A	NP_001352045.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEAL2	ENST00000450053.8	TSL:2 MANE Select	c.6801+21A>C		intron	N/A	ENSP00000415034.2
	NBEAL2	ENST00000416683.5	TSL:1	c.4662+21A>C		intron	N/A	ENSP00000410405.1
	NBEAL2	ENST00000443829.5	TSL:1	c.1905+21A>C		intron	N/A	ENSP00000414560.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37661 AN: 152088 Hom.: 5692 Cov.: 33

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.241

GnomAD2 exomes AF: 0.300 AC: 74537 AN: 248668 AF XY: 0.307

Gnomad AFR exome AF: 0.0703

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.286

Gnomad EAS exome AF: 0.257

Gnomad FIN exome AF: 0.328

Gnomad NFE exome AF: 0.332

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.324 AC: 472864 AN: 1460194 Hom.: 78256 Cov.: 38 AF XY: 0.325 AC XY: 236038 AN XY: 726316

African (AFR) AF: 0.0596 AC: 1994 AN: 33456

American (AMR) AF: 0.255 AC: 11405 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 7530 AN: 26134

East Asian (EAS) AF: 0.283 AC: 11224 AN: 39690

South Asian (SAS) AF: 0.347 AC: 29966 AN: 86242

European-Finnish (FIN) AF: 0.320 AC: 16911 AN: 52808

Middle Eastern (MID) AF: 0.247 AC: 1422 AN: 5768

European-Non Finnish (NFE) AF: 0.337 AC: 373891 AN: 1111056

Other (OTH) AF: 0.307 AC: 18521 AN: 60326

GnomAD4 genome AF: 0.247 AC: 37657 AN: 152208 Hom.: 5692 Cov.: 33 AF XY: 0.247 AC XY: 18371 AN XY: 74398

African (AFR) AF: 0.0725 AC: 3014 AN: 41566

American (AMR) AF: 0.242 AC: 3703 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3470

East Asian (EAS) AF: 0.270 AC: 1396 AN: 5170

South Asian (SAS) AF: 0.352 AC: 1695 AN: 4822

European-Finnish (FIN) AF: 0.324 AC: 3429 AN: 10578

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22630 AN: 67986

Other (OTH) AF: 0.237 AC: 501 AN: 2116

Alfa AF: 0.297 Hom.: 2894

Bravo AF: 0.231

Asia WGS AF: 0.300 AC: 1040 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.85
CADD	Benign	0.80
DANN	Benign	0.51
PhyloP100		0.29
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: rs13081418; hg19: chr3-47047358; COSMIC: COSV52755512; COSMIC: COSV52755512;