Variant 4-121816718-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001237.5(CCNA2):c.*920T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.02 in 1,496,656 control chromosomes in the GnomAD database, including 2,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 875 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1359 hom. )

Consequence

CCNA2
NM_001237.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.997

Variant links:

Genes affected

CCNA2 (HGNC:1578): (cyclin A2) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members function as regulators of the cell cycle. This protein binds and activates cyclin-dependent kinase 2 and thus promotes transition through G1/S and G2/M. [provided by RefSeq, Aug 2016]

CCNA2 links:

EXOSC9 (HGNC:9137): (exosome component 9) This gene encodes a component of the human exosome, a exoribonuclease complex which processes and degrades RNA in the nucleus and cytoplasm. This component may play a role in mRNA degradation and the polymyositis/scleroderma autoantigen complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

EXOSC9 links:

EXOSC9 (HGNC:):

EXOSC9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 4-121816718-A-G is Benign according to our data. Variant chr4-121816718-A-G is described in ClinVar as [Benign]. Clinvar id is 1229339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
CCNA2	NM_001237.5 linkuse as main transcript	c.*920T>C	3_prime_UTR_variant	8/8	ENST00000274026.10	NP_001228.2	P20248
EXOSC9	NM_005033.3 linkuse as main transcript	c.1236-54A>G	intron_variant		ENST00000243498.10	NP_005024.2	Q06265-1
EXOSC9	NM_001034194.2 linkuse as main transcript	c.1287-54A>G	intron_variant			NP_001029366.1	Q06265-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNA2	ENST00000274026 linkuse as main transcript	c.*920T>C		3_prime_UTR_variant	8/8	1	NM_001237.5	ENSP00000274026.5		P20248
EXOSC9	ENST00000243498.10 linkuse as main transcript	c.1236-54A>G		intron_variant		1	NM_005033.3	ENSP00000243498.5		Q06265-1

Frequencies

GnomAD3 genomes

AF:

0.0654

AC:

9952

AN:

152140

Hom.:

874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.0828

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00278

Gnomad OTH

AF:

0.0440

GnomAD4 exome

AF:

0.0149

AC:

20010

AN:

1344398

Hom.:

1359

Cov.:

AF XY:

0.0156

AC XY:

10363

AN XY:

664166

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.0139

Gnomad4 ASJ exome

AF:

0.000403

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.0671

Gnomad4 FIN exome

AF:

0.00579

Gnomad4 NFE exome

AF:

0.00192

Gnomad4 OTH exome

AF:

0.0307

GnomAD4 genome

AF:

0.0655

AC:

9972

AN:

152258

Hom.:

875

Cov.:

AF XY:

0.0671

AC XY:

4994

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.189

Gnomad4 AMR

AF:

0.0245

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.194

Gnomad4 SAS

AF:

0.0831

Gnomad4 FIN

AF:

0.00565

Gnomad4 NFE

AF:

0.00278

Gnomad4 OTH

AF:

0.0445

Alfa

AF:

0.0477

Hom.:

Bravo

AF:

0.0723

Asia WGS

AF:

0.147

AC:

509

AN:

3474

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 submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.0

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over