chr8-22606184-C-G

Variant names:

• chr8-22606184-C-G
• rs2291230
• NM_001393997.1:c.150+8C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001393997.1(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 NM_001393997.1 splice_region, intron
• Scores: Splicing: ADA: 0.00006416
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.727

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCAR2	NM_001393997.1	c.150+8C>G		splice_region_variant, intron_variant	Intron 3 of 20	ENST00000308511.9	NP_001380926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCAR2	ENST00000308511.9	c.150+8C>G		splice_region_variant, intron_variant	Intron 3 of 20	1	NM_001393997.1	ENSP00000310670.4

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62884 AN: 151860 Hom.: 13956 Cov.: 32

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

GnomAD2 exomes AF: 0.363 AC: 91160 AN: 251350 AF XY: 0.367

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 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.: 32 AF XY: 0.366 AC XY: 264648 AN XY: 722618

Gnomad4 AFR exome AF: 0.577 AC: 19214 AN: 33278

Gnomad4 AMR exome AF: 0.267 AC: 11951 AN: 44708

Gnomad4 ASJ exome AF: 0.367 AC: 9559 AN: 26062

Gnomad4 EAS exome AF: 0.307 AC: 12182 AN: 39652

Gnomad4 SAS exome AF: 0.439 AC: 37770 AN: 86016

Gnomad4 FIN exome AF: 0.318 AC: 16962 AN: 53378

Gnomad4 NFE exome AF: 0.359 AC: 395269 AN: 1102178

Gnomad4 Remaining exome AF: 0.373 AC: 22392 AN: 60090

GnomAD4 genome AF: 0.414 AC: 62959 AN: 151978 Hom.: 13989 Cov.: 32 AF XY: 0.410 AC XY: 30424 AN XY: 74276

Gnomad4 AFR AF: 0.571 AC: 0.571143 AN: 0.571143

Gnomad4 AMR AF: 0.349 AC: 0.348564 AN: 0.348564

Gnomad4 ASJ AF: 0.361 AC: 0.361095 AN: 0.361095

Gnomad4 EAS AF: 0.279 AC: 0.279173 AN: 0.279173

Gnomad4 SAS AF: 0.449 AC: 0.448526 AN: 0.448526

Gnomad4 FIN AF: 0.307 AC: 0.307124 AN: 0.307124

Gnomad4 NFE AF: 0.363 AC: 0.362927 AN: 0.362927

Gnomad4 OTH AF: 0.386 AC: 0.386148 AN: 0.386148

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

Submissions by phenotype

CCAR2-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	11
DANN	Benign	0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2291230; hg19: chr8-22463697; COSMIC: COSV51515275; COSMIC: COSV51515275;