rs115611407

Variant names:

• chr3-46995088-G-A
• rs115611407
• NM_015175.3:c.1353G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-46995088-G-A
• chr3-46995088-G-C
• chr3-46995088-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015175.3(NBEAL2):​c.1353G>A​(p.Pro451Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 1,567,158 control chromosomes in the GnomAD database, including 1,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (232 hom., cov: 33)
  • Exomes 𝑓: 0.027 (1683 hom.)
• Consequence: NBEAL2 NM_015175.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.77
• Publications: 10 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-46995088-G-A is Benign according to our data. Variant chr3-46995088-G-A is described in ClinVar as Benign. ClinVar VariationId is 260578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.77 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.123 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.1353G>A	p.Pro451Pro	synonymous	Exon 13 of 54	NP_055990.1	Q6ZNJ1-1
	NBEAL2	NM_001365116.2		c.1251G>A	p.Pro417Pro	synonymous	Exon 12 of 53	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.1353G>A	p.Pro451Pro	synonymous	Exon 13 of 54	ENSP00000415034.2	Q6ZNJ1-1
	NBEAL2	ENST00000651747.1		c.1251G>A	p.Pro417Pro	synonymous	Exon 12 of 53	ENSP00000499216.1	A0A494C1V1
	NBEAL2	ENST00000933460.1		c.1272G>A	p.Pro424Pro	synonymous	Exon 12 of 52	ENSP00000603519.1

Frequencies

GnomAD3 genomes AF: 0.0311 AC: 4739 AN: 152226 Hom.: 231 Cov.: 33

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0499

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0287

GnomAD2 exomes AF: 0.0623 AC: 11672 AN: 187312 AF XY: 0.0547

Gnomad AFR exome AF: 0.0101

Gnomad AMR exome AF: 0.221

Gnomad ASJ exome AF: 0.0624

Gnomad EAS exome AF: 0.133

Gnomad FIN exome AF: 0.0162

Gnomad NFE exome AF: 0.0175

Gnomad OTH exome AF: 0.0489

GnomAD4 exome AF: 0.0272 AC: 38427 AN: 1414814 Hom.: 1683 Cov.: 32 AF XY: 0.0270 AC XY: 18863 AN XY: 698542

African (AFR) AF: 0.00878 AC: 284 AN: 32348

American (AMR) AF: 0.205 AC: 8004 AN: 39116

Ashkenazi Jewish (ASJ) AF: 0.0618 AC: 1573 AN: 25444

East Asian (EAS) AF: 0.142 AC: 5263 AN: 36952

South Asian (SAS) AF: 0.0419 AC: 3383 AN: 80816

European-Finnish (FIN) AF: 0.0182 AC: 892 AN: 49120

Middle Eastern (MID) AF: 0.0414 AC: 236 AN: 5706

European-Non Finnish (NFE) AF: 0.0157 AC: 17046 AN: 1086920

Other (OTH) AF: 0.0299 AC: 1746 AN: 58392

GnomAD4 genome AF: 0.0312 AC: 4754 AN: 152344 Hom.: 232 Cov.: 33 AF XY: 0.0339 AC XY: 2527 AN XY: 74498

African (AFR) AF: 0.0105 AC: 436 AN: 41578

American (AMR) AF: 0.116 AC: 1782 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0616 AC: 214 AN: 3472

East Asian (EAS) AF: 0.132 AC: 683 AN: 5190

South Asian (SAS) AF: 0.0499 AC: 241 AN: 4826

European-Finnish (FIN) AF: 0.0145 AC: 154 AN: 10624

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0171 AC: 1165 AN: 68030

Other (OTH) AF: 0.0288 AC: 61 AN: 2116

Alfa AF: 0.0167 Hom.: 23

Bravo AF: 0.0406

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Gray platelet syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.13
DANN	Benign	0.49
PhyloP100		-4.8
PromoterAI		0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=94/6	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: rs115611407; hg19: chr3-47036578; COSMIC: COSV52757093; COSMIC: COSV52757093;