3-46979634-A-G

Position:

• chr3-46979634-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144716.6(CCDC12):​c.-73+2298T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 305,436 control chromosomes in the GnomAD database, including 44,634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19812 hom., cov: 33)
  • Exomes 𝑓: 0.57 (24822 hom.)
• Consequence: CCDC12 NM_144716.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.71

Genes affected

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]

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 3-46979634-A-G is Benign according to our data. Variant chr3-46979634-A-G is described in ClinVar as [Benign]. Clinvar id is 1248264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBEAL2	NM_015175.3			upstream_gene_variant		ENST00000450053.8	NP_055990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBEAL2	ENST00000450053.8			upstream_gene_variant		2	NM_015175.3	ENSP00000415034	P2

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74589 AN: 151926 Hom.: 19788 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.566 AC: 86808 AN: 153390 Hom.: 24822 Cov.: 0 AF XY: 0.567 AC XY: 44750 AN XY: 78986

Gnomad4 AFR exome AF: 0.292

Gnomad4 AMR exome AF: 0.559

Gnomad4 ASJ exome AF: 0.539

Gnomad4 EAS exome AF: 0.541

Gnomad4 SAS exome AF: 0.556

Gnomad4 FIN exome AF: 0.604

Gnomad4 NFE exome AF: 0.581

Gnomad4 OTH exome AF: 0.537

GnomAD4 genome AF: 0.491 AC: 74646 AN: 152046 Hom.: 19812 Cov.: 33 AF XY: 0.492 AC XY: 36582 AN XY: 74334

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.504

Alfa AF: 0.403 Hom.: 1230

Bravo AF: 0.475

Asia WGS AF: 0.586 AC: 2035 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.4
DANN	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs13062681; hg19: chr3-47021124;