chr3-46979700-C-T

Variant names:

• chr3-46979700-C-T
• rs886058587
• NM_015175.3:c.-162C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015175.3(NBEAL2):​c.-162C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000963 in 311,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: NBEAL2 NM_015175.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.252
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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.-162C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 54	NP_055990.1	Q6ZNJ1-1
	NBEAL2	NM_015175.3	MANE Select	c.-162C>T		5_prime_UTR	Exon 1 of 54	NP_055990.1	Q6ZNJ1-1
	CCDC12	NM_144716.6		c.-73+2232G>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.-162C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 54	ENSP00000415034.2	Q6ZNJ1-1
	NBEAL2	ENST00000450053.8	TSL:2 MANE Select	c.-162C>T		5_prime_UTR	Exon 1 of 54	ENSP00000415034.2	Q6ZNJ1-1
	CCDC12	ENST00000292314.6	TSL:5	c.-73+2232G>A		intron	N/A	ENSP00000292314.2	J3KR35

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000126 AC: 2 AN: 159264 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 82380

African (AFR) AF: 0.00 AC: 0 AN: 3908

American (AMR) AF: 0.00 AC: 0 AN: 4504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5314

East Asian (EAS) AF: 0.00 AC: 0 AN: 15718

South Asian (SAS) AF: 0.00 AC: 0 AN: 1594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 820

European-Non Finnish (NFE) AF: 0.0000197 AC: 2 AN: 101612

Other (OTH) AF: 0.00 AC: 0 AN: 9928

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Gray platelet syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		-0.25
PromoterAI		-0.074	Neutral

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: rs886058587; hg19: chr3-47021190;