10-68726568-T-G

Variant summary

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

The NM_018237.4(CCAR1):c.73+3991T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,952 control chromosomes in the GnomAD database, including 10,651 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 0.36 (10651 hom., cov: 30)
• Consequence: CCAR1 NM_018237.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

Genes affected

CCAR1 (HGNC:24236): (cell division cycle and apoptosis regulator 1) Enables RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; nuclear receptor coactivator activity; and transcription corepressor activity. Involved in positive regulation of cell migration and positive regulation of cell population proliferation. Acts upstream of or within positive regulation of apoptotic process. Located in nuclear envelope lumen. [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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCAR1	NM_018237.4	c.73+3991T>G		intron_variant		ENST00000265872.11
CCAR1	NM_001282959.2	c.73+3991T>G		intron_variant
CCAR1	NM_001282960.2	c.73+3991T>G		intron_variant
CCAR1	NR_104262.2	n.173+3991T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCAR1	ENST00000265872.11	c.73+3991T>G		intron_variant		1	NM_018237.4	P1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55068 AN: 151834 Hom.: 10650 Cov.: 30

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.395

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.362 AC: 55069 AN: 151952 Hom.: 10651 Cov.: 30 AF XY: 0.358 AC XY: 26598 AN XY: 74242

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.394

Alfa AF: 0.437 Hom.: 28671

Bravo AF: 0.360

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.88
Dann	Benign	0.50

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: rs1782322; hg19: chr10-70486325;