Variant 8-22606184-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000308511.9(CCAR2):c.150+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,603,092 control chromosomes in the GnomAD database, including 112,173 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.41 ( 13989 hom., cov: 32)

Exomes 𝑓: 0.36 ( 98184 hom. )

Consequence

CCAR2
ENST00000308511.9 splice_region, intron

Scores

Splicing: ADA: 0.00006416

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.727

Variant links:

Genes affected

CCAR2 (HGNC:23360): (cell cycle and apoptosis regulator 2) Enables RNA polymerase II complex binding activity and enzyme inhibitor activity. Involved in several processes, including regulation of cellular protein metabolic process; regulation of signal transduction; and regulation of transcription, DNA-templated. Located in several cellular components, including mitochondrial matrix; nucleoplasm; and spindle. Part of DBIRD complex. [provided by Alliance of Genome Resources, Apr 2022]

CCAR2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 8-22606184-C-G is Benign according to our data. Variant chr8-22606184-C-G is described in ClinVar as [Benign]. Clinvar id is 3059619.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCAR2	NM_001393997.1 linkuse as main transcript	c.150+8C>G		splice_region_variant, intron_variant		ENST00000308511.9	NP_001380926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCAR2	ENST00000308511.9 linkuse as main transcript	c.150+8C>G		splice_region_variant, intron_variant		1	NM_001393997.1	ENSP00000310670	P1	Q8N163-1

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62884

AN:

151860

Hom.:

13956

Cov.:

show subpopulations

Gnomad AFR

AF:

0.571

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.361

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.385

GnomAD3 exomes

AF:

0.363

AC:

91160

AN:

251350

Hom.:

17435

AF XY:

0.367

AC XY:

49854

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.572

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.365

Gnomad EAS exome

AF:

0.271

Gnomad SAS exome

AF:

0.444

Gnomad FIN exome

AF:

0.320

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.359

GnomAD4 exome

AF:

0.363

AC:

527282

AN:

1451114

Hom.:

98184

Cov.:

AF XY:

0.366

AC XY:

264648

AN XY:

722618

show subpopulations

Gnomad4 AFR exome

AF:

0.577

Gnomad4 AMR exome

AF:

0.267

Gnomad4 ASJ exome

AF:

0.367

Gnomad4 EAS exome

AF:

0.307

Gnomad4 SAS exome

AF:

0.439

Gnomad4 FIN exome

AF:

0.318

Gnomad4 NFE exome

AF:

0.359

Gnomad4 OTH exome

AF:

0.373

GnomAD4 genome

AF:

0.414

AC:

62959

AN:

151978

Hom.:

13989

Cov.:

AF XY:

0.410

AC XY:

30424

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.571

Gnomad4 AMR

AF:

0.349

Gnomad4 ASJ

AF:

0.361

Gnomad4 EAS

AF:

0.279

Gnomad4 SAS

AF:

0.449

Gnomad4 FIN

AF:

0.307

Gnomad4 NFE

AF:

0.363

Gnomad4 OTH

AF:

0.386

Alfa

AF:

0.375

Hom.:

3575

Bravo

AF:

0.417

Asia WGS

AF:

0.413

AC:

1436

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CCAR2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000064

dbscSNV1_RF

Benign

0.0

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