8-22606551-T-C

Position:

• chr8-22606551-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCAR2	NM_001393997.1	c.151-56T>C		intron_variant		ENST00000308511.9	NP_001380926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCAR2	ENST00000308511.9	c.151-56T>C		intron_variant		1	NM_001393997.1	ENSP00000310670.4

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45978 AN: 151684 Hom.: 7238 Cov.: 32

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

GnomAD3 exomes AF: 0.300 AC: 70532 AN: 234728 Hom.: 10795 AF XY: 0.308 AC XY: 39075 AN XY: 127054

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 SAS exome AF: 0.359

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.: 17 AF XY: 0.322 AC XY: 199474 AN XY: 619310

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.317

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.358

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.329

Gnomad4 OTH exome AF: 0.317

GnomAD4 genome AF: 0.303 AC: 46006 AN: 151804 Hom.: 7243 Cov.: 32 AF XY: 0.299 AC XY: 22158 AN XY: 74194

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.300

Alfa AF: 0.289 Hom.: 2806

Bravo AF: 0.299

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.51

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

Other links and lift over

dbSNP: rs2291232; hg19: chr8-22464064; COSMIC: COSV51515404; COSMIC: COSV51515404;