3-46979634-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.71
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 UniProt
NBEAL2NM_015175.3 linkuse as main transcript upstream_gene_variant ENST00000450053.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NBEAL2ENST00000450053.8 linkuse as main transcript upstream_gene_variant 2 NM_015175.3 P2Q6ZNJ1-1

Frequencies

GnomAD3 genomes
AF:
0.491
AC:
74589
AN:
151926
Hom.:
19788
Cov.:
33
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs13062681; hg19: chr3-47021124; API