3-46979742-C-T

Variant names:

• chr3-46979742-C-T
• rs1011004600
• NM_015175.3:c.-120C>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.-120C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBEAL2 NM_015175.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• 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=-0.54).

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.-120C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 54	NP_055990.1	Q6ZNJ1-1
	NBEAL2	NM_015175.3	MANE Select	c.-120C>T		5_prime_UTR	Exon 1 of 54	NP_055990.1	Q6ZNJ1-1
	CCDC12	NM_144716.6		c.-73+2190G>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.-120C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 54	ENSP00000415034.2	Q6ZNJ1-1
	NBEAL2	ENST00000450053.8	TSL:2 MANE Select	c.-120C>T		5_prime_UTR	Exon 1 of 54	ENSP00000415034.2	Q6ZNJ1-1
	NBEAL2	ENST00000952756.1		c.-120C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 52	ENSP00000622815.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 169418 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 87718

African (AFR) AF: 0.00 AC: 0 AN: 4184

American (AMR) AF: 0.00 AC: 0 AN: 4680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5668

East Asian (EAS) AF: 0.00 AC: 0 AN: 16546

South Asian (SAS) AF: 0.00 AC: 0 AN: 2008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 898

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 108162

Other (OTH) AF: 0.00 AC: 0 AN: 10598

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.96
PhyloP100		-0.055
PromoterAI		0.20	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: rs1011004600; hg19: chr3-47021232;