rs12489851

Variant names:

• chr3-47001748-C-A
• NM_015175.3:c.4704C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-47001748-C-A
• chr3-47001748-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015175.3(NBEAL2):​c.4704C>A​(p.Asn1568Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NBEAL2 NM_015175.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.83

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20352167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEAL2	NM_015175.3	c.4704C>A	p.Asn1568Lys	missense_variant	Exon 30 of 54	ENST00000450053.8	NP_055990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBEAL2	ENST00000450053.8	c.4704C>A	p.Asn1568Lys	missense_variant	Exon 30 of 54	2	NM_015175.3	ENSP00000415034.2
NBEAL2	ENST00000416683.5	c.2565C>A	p.Asn855Lys	missense_variant	Exon 16 of 40	1		ENSP00000410405.1
NBEAL2	ENST00000651747.1	c.4602C>A	p.Asn1534Lys	missense_variant	Exon 29 of 53			ENSP00000499216.1
NBEAL2	ENST00000475689.1	n.549C>A		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461588 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727064

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.54
DANN	Benign	0.97
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.20
Sift	Benign	0.16	T
Polyphen		0.97	D
Vest4		0.48
MutPred		0.36		Gain of ubiquitination at N1568 (P = 0.0238);
MVP		0.26
MPC		0.24
ClinPred		0.95	D
GERP RS		-6.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.086

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-47043238;