10-68771387-C-T

Position:

• chr10-68771387-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018237.4(CCAR1):​c.2480C>T​(p.Pro827Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCAR1 NM_018237.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.05

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]

CCAR1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15958494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCAR1	NM_018237.4	c.2480C>T	p.Pro827Leu	missense_variant	18/25	ENST00000265872.11	NP_060707.2
CCAR1	NM_001282959.2	c.2435C>T	p.Pro812Leu	missense_variant	17/24		NP_001269888.1
CCAR1	NM_001282960.2	c.2435C>T	p.Pro812Leu	missense_variant	17/24		NP_001269889.1
CCAR1	NR_104262.2	n.2369C>T		non_coding_transcript_exon_variant	17/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCAR1	ENST00000265872.11	c.2480C>T	p.Pro827Leu	missense_variant	18/25	1	NM_018237.4	ENSP00000265872.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2023

The c.2480C>T (p.P827L) alteration is located in exon 18 (coding exon 17) of the CCAR1 gene. This alteration results from a C to T substitution at nucleotide position 2480, causing the proline (P) at amino acid position 827 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;.;.
Eigen	Benign	-0.022
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;.;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.97	N;N;N;N
REVEL	Benign	0.046
Sift	Uncertain	0.028	D;D;D;D
Sift4G	Benign	0.41	T;T;T;T
Polyphen		0.13	B;B;.;.
Vest4		0.18
MutPred		0.19		Loss of loop (P = 0.0288);.;.;.;
MVP		0.22
MPC		0.23
ClinPred		0.45	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.083
gMVP		0.047

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-70531144; COSMIC: COSV56274243; COSMIC: COSV56274243;