3-47005686-AG-AGG

Variant names:

• chr3-47005686-A-AG
• rs5848810
• NM_015175.3:c.6692-47dupG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015175.3(NBEAL2):​c.6692-47dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 1,612,066 control chromosomes in the GnomAD database, including 268,688 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (23981 hom., cov: 0)
  • Exomes 𝑓: 0.58 (244707 hom.)
• Consequence: NBEAL2 NM_015175.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.75
• 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 -10 ACMG points.

• BP6: Variant 3-47005686-A-AG is Benign according to our data. Variant chr3-47005686-A-AG is described in ClinVar as Benign. ClinVar VariationId is 260589.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.582 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEAL2	NM_015175.3	MANE Select	c.6692-47dupG		intron	N/A	NP_055990.1
	NBEAL2	NM_001365116.2		c.6590-47dupG		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.6692-47dupG		intron	N/A	ENSP00000415034.2
	NBEAL2	ENST00000416683.5	TSL:1	c.4553-47dupG		intron	N/A	ENSP00000410405.1
	NBEAL2	ENST00000443829.5	TSL:1	c.1796-47dupG		intron	N/A	ENSP00000414560.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84877 AN: 151880 Hom.: 23944 Cov.: 0

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.553

GnomAD4 exome AF: 0.578 AC: 843538 AN: 1460068 Hom.: 244707 Cov.: 40 AF XY: 0.576 AC XY: 418261 AN XY: 726280

African (AFR) AF: 0.518 AC: 17327 AN: 33458

American (AMR) AF: 0.518 AC: 23109 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 13734 AN: 26108

East Asian (EAS) AF: 0.566 AC: 22437 AN: 39674

South Asian (SAS) AF: 0.542 AC: 46749 AN: 86184

European-Finnish (FIN) AF: 0.607 AC: 32033 AN: 52792

Middle Eastern (MID) AF: 0.477 AC: 2749 AN: 5766

European-Non Finnish (NFE) AF: 0.586 AC: 651054 AN: 1111152

Other (OTH) AF: 0.569 AC: 34346 AN: 60328

GnomAD4 genome AF: 0.559 AC: 84965 AN: 151998 Hom.: 23981 Cov.: 0 AF XY: 0.556 AC XY: 41322 AN XY: 74280

African (AFR) AF: 0.517 AC: 21421 AN: 41462

American (AMR) AF: 0.532 AC: 8132 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1844 AN: 3472

East Asian (EAS) AF: 0.555 AC: 2847 AN: 5126

South Asian (SAS) AF: 0.543 AC: 2615 AN: 4814

European-Finnish (FIN) AF: 0.615 AC: 6504 AN: 10574

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39906 AN: 67964

Other (OTH) AF: 0.555 AC: 1170 AN: 2108

Alfa AF: 0.573 Hom.: 3051

Bravo AF: 0.549

Asia WGS AF: 0.611 AC: 2123 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8
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: rs5848810; hg19: chr3-47047176;