3-47005352-G-C

Variant names:

• chr3-47005352-G-C
• rs2305638
• NM_015175.3:c.6560+31G>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.6560+31G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,597,436 control chromosomes in the GnomAD database, including 261,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23417 hom., cov: 34)
  • Exomes 𝑓: 0.57 (238451 hom.)
• Consequence: NBEAL2 NM_015175.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.742
• Publications: 16 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=-0.86).
• BP6: Variant 3-47005352-G-C is Benign according to our data. Variant chr3-47005352-G-C is described in ClinVar as Benign. ClinVar VariationId is 260588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEAL2	NM_015175.3	c.6560+31G>C		intron_variant	Intron 40 of 53	ENST00000450053.8	NP_055990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBEAL2	ENST00000450053.8	c.6560+31G>C		intron_variant	Intron 40 of 53	2	NM_015175.3	ENSP00000415034.2

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83860 AN: 151974 Hom.: 23383 Cov.: 34

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.544

GnomAD2 exomes AF: 0.555 AC: 123627 AN: 222748 AF XY: 0.555

Gnomad AFR exome AF: 0.503

Gnomad AMR exome AF: 0.514

Gnomad ASJ exome AF: 0.529

Gnomad EAS exome AF: 0.545

Gnomad FIN exome AF: 0.613

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.571

GnomAD4 exome AF: 0.573 AC: 828677 AN: 1445344 Hom.: 238451 Cov.: 63 AF XY: 0.572 AC XY: 410238 AN XY: 717684

African (AFR) AF: 0.501 AC: 16588 AN: 33122

American (AMR) AF: 0.513 AC: 21703 AN: 42312

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 13519 AN: 25812

East Asian (EAS) AF: 0.565 AC: 21947 AN: 38866

South Asian (SAS) AF: 0.538 AC: 45530 AN: 84624

European-Finnish (FIN) AF: 0.605 AC: 30576 AN: 50512

Middle Eastern (MID) AF: 0.471 AC: 2709 AN: 5750

European-Non Finnish (NFE) AF: 0.582 AC: 642376 AN: 1104568

Other (OTH) AF: 0.564 AC: 33729 AN: 59778

GnomAD4 genome AF: 0.552 AC: 83944 AN: 152092 Hom.: 23417 Cov.: 34 AF XY: 0.549 AC XY: 40844 AN XY: 74352

African (AFR) AF: 0.501 AC: 20773 AN: 41490

American (AMR) AF: 0.526 AC: 8045 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1831 AN: 3472

East Asian (EAS) AF: 0.555 AC: 2858 AN: 5146

South Asian (SAS) AF: 0.541 AC: 2609 AN: 4824

European-Finnish (FIN) AF: 0.614 AC: 6497 AN: 10578

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39655 AN: 67962

Other (OTH) AF: 0.546 AC: 1155 AN: 2114

Alfa AF: 0.563 Hom.: 4454

Bravo AF: 0.543

Asia WGS AF: 0.607 AC: 2106 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Gray platelet syndrome Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.74
DANN	Benign	0.47
PhyloP100		-0.74
PromoterAI		0.029	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2305638; hg19: chr3-47046842; COSMIC: COSV52755505; COSMIC: COSV52755505;