3-46979786-G-T

Variant names:

• chr3-46979786-G-T
• rs886058588
• NM_015175.3:c.-76G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015175.3(NBEAL2):​c.-76G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000442 in 226,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000044 (0 hom.)
• Consequence: NBEAL2 NM_015175.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• Publications: 0 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]

CCDC12 (HGNC:28332): (coiled-coil domain containing 12) Predicted to be part of U2-type spliceosomal complex and post-mRNA release spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).

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.-76G>T		5_prime_UTR	Exon 1 of 54	NP_055990.1	Q6ZNJ1-1
	CCDC12	NM_144716.6		c.-73+2146C>A		intron	N/A	NP_653317.2	J3KR35

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEAL2	ENST00000450053.8	TSL:2 MANE Select	c.-76G>T		5_prime_UTR	Exon 1 of 54	ENSP00000415034.2	Q6ZNJ1-1
	NBEAL2	ENST00000952756.1		c.-76G>T		5_prime_UTR	Exon 1 of 52	ENSP00000622815.1
	CCDC12	ENST00000292314.6	TSL:5	c.-73+2146C>A		intron	N/A	ENSP00000292314.2	J3KR35

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000442 AC: 1 AN: 226256 Hom.: 0 Cov.: 0 AF XY: 0.00000835 AC XY: 1 AN XY: 119810

African (AFR) AF: 0.00 AC: 0 AN: 5584

American (AMR) AF: 0.00 AC: 0 AN: 5960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7358

East Asian (EAS) AF: 0.00 AC: 0 AN: 19610

South Asian (SAS) AF: 0.000150 AC: 1 AN: 6652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1108

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 146222

Other (OTH) AF: 0.00 AC: 0 AN: 13870

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Benign	0.95
PhyloP100		2.1
PromoterAI		-0.079	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs886058588; hg19: chr3-47021276;