rs749512

Variant names:

• chr3-46994410-C-T
• rs749512
• NM_015175.3:c.1198-45C>T

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.1198-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,521,638 control chromosomes in the GnomAD database, including 102,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8431 hom., cov: 33)
  • Exomes 𝑓: 0.37 (94100 hom.)
• Consequence: NBEAL2 NM_015175.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0960
• Publications: 15 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=-0.84).
• BP6: Variant 3-46994410-C-T is Benign according to our data. Variant chr3-46994410-C-T is described in ClinVar as Benign. ClinVar VariationId is 260576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEAL2	NM_015175.3	c.1198-45C>T		intron_variant	Intron 11 of 53	ENST00000450053.8	NP_055990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBEAL2	ENST00000450053.8	c.1198-45C>T		intron_variant	Intron 11 of 53	2	NM_015175.3	ENSP00000415034.2
NBEAL2	ENST00000651747.1	c.1096-45C>T		intron_variant	Intron 10 of 52			ENSP00000499216.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49287 AN: 152002 Hom.: 8432 Cov.: 33

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.350

GnomAD2 exomes AF: 0.341 AC: 54711 AN: 160286 AF XY: 0.351

Gnomad AFR exome AF: 0.212

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.375

Gnomad EAS exome AF: 0.316

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.378

Gnomad OTH exome AF: 0.352

GnomAD4 exome AF: 0.367 AC: 503224 AN: 1369518 Hom.: 94100 Cov.: 26 AF XY: 0.370 AC XY: 250650 AN XY: 677884

African (AFR) AF: 0.221 AC: 6867 AN: 31118

American (AMR) AF: 0.250 AC: 9198 AN: 36732

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 9456 AN: 25000

East Asian (EAS) AF: 0.289 AC: 10414 AN: 36018

South Asian (SAS) AF: 0.395 AC: 31192 AN: 79032

European-Finnish (FIN) AF: 0.357 AC: 16909 AN: 47346

Middle Eastern (MID) AF: 0.439 AC: 2482 AN: 5654

European-Non Finnish (NFE) AF: 0.376 AC: 395869 AN: 1051658

Other (OTH) AF: 0.366 AC: 20837 AN: 56960

GnomAD4 genome AF: 0.324 AC: 49282 AN: 152120 Hom.: 8431 Cov.: 33 AF XY: 0.327 AC XY: 24309 AN XY: 74338

African (AFR) AF: 0.224 AC: 9314 AN: 41508

American (AMR) AF: 0.320 AC: 4894 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1312 AN: 3472

East Asian (EAS) AF: 0.312 AC: 1611 AN: 5166

South Asian (SAS) AF: 0.386 AC: 1861 AN: 4816

European-Finnish (FIN) AF: 0.357 AC: 3778 AN: 10570

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25178 AN: 67982

Other (OTH) AF: 0.348 AC: 736 AN: 2112

Alfa AF: 0.358 Hom.: 7173

Bravo AF: 0.313

Asia WGS AF: 0.303 AC: 1057 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.1
DANN	Benign	0.63
PhyloP100		0.096
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)		0.010		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: rs749512; hg19: chr3-47035900; COSMIC: COSV52756708; COSMIC: COSV52756708;