NM_015175.3:c.-120C>G

Variant names:

• chr3-46979742-C-G
• rs1011004600
• NM_015175.3:c.-120C>G

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>G variant causes a 5 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NBEAL2 NM_015175.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=-0.57).

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>G		5_prime_UTR	Exon 1 of 54	NP_055990.1	Q6ZNJ1-1
	CCDC12	NM_144716.6		c.-73+2190G>C		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>G		5_prime_UTR	Exon 1 of 54	ENSP00000415034.2	Q6ZNJ1-1
	NBEAL2	ENST00000952756.1		c.-120C>G		5_prime_UTR	Exon 1 of 52	ENSP00000622815.1
	CCDC12	ENST00000292314.6	TSL:5	c.-73+2190G>C		intron	N/A	ENSP00000292314.2	J3KR35

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

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	-0.57
CADD	Benign	16
DANN	Benign	0.87
PhyloP100		-0.055
PromoterAI		0.24	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: rs1011004600; hg19: chr3-47021232;