rs11928558

Variant names:

• chr3-47002632-A-T
• rs11928558
• NM_015175.3:c.5302-13A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-47002632-A-T
• chr3-47002632-A-C
• chr3-47002632-A-G

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.5302-13A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,608,510 control chromosomes in the GnomAD database, including 790,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (69431 hom., cov: 34)
  • Exomes 𝑓: 0.99 (720942 hom.)
• Consequence: NBEAL2 NM_015175.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.19
• Publications: 8 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=-0.82).
• BP6: Variant 3-47002632-A-T is Benign according to our data. Variant chr3-47002632-A-T is described in ClinVar as Benign. ClinVar VariationId is 260584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.5302-13A>T		intron	N/A	NP_055990.1	Q6ZNJ1-1
	NBEAL2	NM_001365116.2		c.5200-13A>T		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.5302-13A>T		intron	N/A	ENSP00000415034.2	Q6ZNJ1-1
	NBEAL2	ENST00000416683.5	TSL:1	c.3163-13A>T		intron	N/A	ENSP00000410405.1	H0Y764
	NBEAL2	ENST00000443829.5	TSL:1	c.406-13A>T		intron	N/A	ENSP00000414560.1	H7C3Y7

Frequencies

GnomAD3 genomes AF: 0.952 AC: 144839 AN: 152172 Hom.: 69385 Cov.: 34

Gnomad AFR AF: 0.834

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.994

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.961

GnomAD2 exomes AF: 0.989 AC: 232179 AN: 234872 AF XY: 0.991

Gnomad AFR exome AF: 0.833

Gnomad AMR exome AF: 0.993

Gnomad ASJ exome AF: 0.994

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.993

GnomAD4 exome AF: 0.995 AC: 1448547 AN: 1456220 Hom.: 720942 Cov.: 75 AF XY: 0.995 AC XY: 720669 AN XY: 724048

African (AFR) AF: 0.834 AC: 27874 AN: 33426

American (AMR) AF: 0.991 AC: 43674 AN: 44076

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 25796 AN: 25972

East Asian (EAS) AF: 1.00 AC: 39600 AN: 39600

South Asian (SAS) AF: 1.00 AC: 85562 AN: 85578

European-Finnish (FIN) AF: 1.00 AC: 51161 AN: 51164

Middle Eastern (MID) AF: 0.986 AC: 5683 AN: 5762

European-Non Finnish (NFE) AF: 0.999 AC: 1109684 AN: 1110456

Other (OTH) AF: 0.989 AC: 59513 AN: 60186

GnomAD4 genome AF: 0.952 AC: 144945 AN: 152290 Hom.: 69431 Cov.: 34 AF XY: 0.954 AC XY: 71019 AN XY: 74470

African (AFR) AF: 0.834 AC: 34643 AN: 41536

American (AMR) AF: 0.982 AC: 15040 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 3450 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5166 AN: 5166

South Asian (SAS) AF: 1.00 AC: 4830 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67954 AN: 68026

Other (OTH) AF: 0.961 AC: 2032 AN: 2114

Alfa AF: 0.978 Hom.: 13375

Bravo AF: 0.945

Asia WGS AF: 0.993 AC: 3455 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	-0.82
CADD	Benign	0.10
DANN	Benign	0.45
PhyloP100		-1.2
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)		0.0		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: rs11928558; hg19: chr3-47044122;