Genetic Variant CCAR2:c.151-56T>C (chr8-22606551-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001393997.1(CCAR2):c.151-56T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,374,288 control chromosomes in the GnomAD database, including 70,485 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7243 hom., cov: 32)

Exomes 𝑓: 0.32 ( 63242 hom. )

Consequence

CCAR2
NM_001393997.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.65

Publications

11 publications found

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

new If you want to explore the variant's impact on the transcript NM_001393997.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393997.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCAR2	NM_001393997.1	MANE Select	c.151-56T>C	intron	N/A	NP_001380926.1	Q8N163-1
CCAR2	NM_021174.6		c.151-56T>C	intron	N/A	NP_066997.3
CCAR2	NM_001363068.2		c.151-56T>C	intron	N/A	NP_001349997.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCAR2	ENST00000308511.9	TSL:1 MANE Select	c.151-56T>C	intron	N/A	ENSP00000310670.4	Q8N163-1
CCAR2	ENST00000389279.7	TSL:1	c.151-56T>C	intron	N/A	ENSP00000373930.3	Q8N163-1
CCAR2	ENST00000952221.1		c.151-56T>C	intron	N/A	ENSP00000622280.1

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

45978

AN:

151684

Hom.:

7238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.299

GnomAD2 exomes

AF:

0.300

AC:

70532

AN:

234728

AF XY:

0.308

show subpopulations

Gnomad AFR exome

AF:

0.286

Gnomad AMR exome

AF:

0.225

Gnomad ASJ exome

AF:

0.312

Gnomad EAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.263

Gnomad NFE exome

AF:

0.334

Gnomad OTH exome

AF:

0.303

GnomAD4 exome

AF:

0.320

AC:

390636

AN:

1222484

Hom.:

63242

Cov.:

AF XY:

0.322

AC XY:

199474

AN XY:

619310

show subpopulations

African (AFR)

AF:

0.286

AC:

8231

AN:

28752

American (AMR)

AF:

0.232

AC:

9922

AN:

42736

Ashkenazi Jewish (ASJ)

AF:

0.317

AC:

7783

AN:

24560

East Asian (EAS)

AF:

0.229

AC:

8784

AN:

38308

South Asian (SAS)

AF:

0.358

AC:

28873

AN:

80550

European-Finnish (FIN)

AF:

0.260

AC:

13742

AN:

52786

Middle Eastern (MID)

AF:

0.258

AC:

1301

AN:

5042

European-Non Finnish (NFE)

AF:

0.329

AC:

295404

AN:

897456

Other (OTH)

AF:

0.317

AC:

16596

AN:

52294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

14641

29282

43922

58563

73204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8616

17232

25848

34464

43080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.303

AC:

46006

AN:

151804

Hom.:

7243

Cov.:

AF XY:

0.299

AC XY:

22158

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.282

AC:

11675

AN:

41338

American (AMR)

AF:

0.290

AC:

4429

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

1060

AN:

3466

East Asian (EAS)

AF:

0.197

AC:

1020

AN:

5170

South Asian (SAS)

AF:

0.369

AC:

1776

AN:

4814

European-Finnish (FIN)

AF:

0.253

AC:

2666

AN:

10520

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.329

AC:

22376

AN:

67928

Other (OTH)

AF:

0.300

AC:

632

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1631

3262

4894

6525

8156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.297

Hom.:

4120

Bravo

AF:

0.299

Asia WGS

AF:

0.307

AC:

1067

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.12

(source)

DANN

Benign

0.51

PhyloP100

-2.6

PromoterAI

0.023

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over