Variant chr8-22608000-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001393997.1(CCAR2):c.519T>G(p.Leu173=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,613,982 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 6 hom. )

Consequence

CCAR2
NM_001393997.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.124

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 8-22608000-T-G is Benign according to our data. Variant chr8-22608000-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3053112.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.124 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCAR2	NM_001393997.1 linkuse as main transcript	c.519T>G	p.Leu173=	synonymous_variant	7/21	ENST00000308511.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCAR2	ENST00000308511.9 linkuse as main transcript	c.519T>G	p.Leu173=	synonymous_variant	7/21	1	NM_001393997.1	P1	Q8N163-1

Frequencies

GnomAD3 genomes

AF:

0.00200

AC:

304

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0111

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00234

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00210

AC:

529

AN:

251466

Hom.:

AF XY:

0.00211

AC XY:

287

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00915

Gnomad NFE exome

AF:

0.00265

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00237

AC:

3470

AN:

1461692

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

1732

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.00735

Gnomad4 NFE exome

AF:

0.00264

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00200

AC:

304

AN:

152290

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

174

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0111

Gnomad4 NFE

AF:

0.00234

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00225

Hom.:

Bravo

AF:

0.00133

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CCAR2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 2019

This variant is classified as likely 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

-0.48

CADD

Benign

9.5

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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