rs73075647

chr3-47001896-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015175.3(NBEAL2):c.4783-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,605,488 control chromosomes in the GnomAD database, including 28,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2296 hom., cov: 33)
  • Exomes 𝑓: 0.18 (25798 hom.)
• Consequence: NBEAL2 NM_015175.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.847

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-47001896-C-T is Benign according to our data. Variant chr3-47001896-C-T is described in ClinVar as [Benign]. Clinvar id is 260581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBEAL2	NM_015175.3	c.4783-24C>T		intron_variant		ENST00000450053.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBEAL2	ENST00000450053.8	c.4783-24C>T		intron_variant		2	NM_015175.3	P2
NBEAL2	ENST00000416683.5	c.2646-24C>T		intron_variant		1
NBEAL2	ENST00000651747.1	c.4681-24C>T		intron_variant				A2
NBEAL2	ENST00000475689.1	n.628-24C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25504 AN: 152034 Hom.: 2293 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0972

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.173

GnomAD3 exomes AF: 0.152 AC: 37637 AN: 246880 Hom.: 3472 AF XY: 0.155 AC XY: 20750 AN XY: 134136

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.0860

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.000334

Gnomad SAS exome AF: 0.0967

Gnomad FIN exome AF: 0.168

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.183 AC: 265437 AN: 1453334 Hom.: 25798 Cov.: 34 AF XY: 0.181 AC XY: 130586 AN XY: 721212

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.0904

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.000304

Gnomad4 SAS exome AF: 0.0970

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.168 AC: 25502 AN: 152154 Hom.: 2296 Cov.: 33 AF XY: 0.163 AC XY: 12092 AN XY: 74394

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0977

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.171

Alfa AF: 0.190 Hom.: 495

Bravo AF: 0.162

Asia WGS AF: 0.0450 AC: 159 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.5
Dann	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs73075647; hg19: chr3-47043386; COSMIC: COSV52756728; COSMIC: COSV52756728;