Variant 10-68749637-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_018237.4(CCAR1):c.1070G>T(p.Arg357Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CCAR1
NM_018237.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.14

Variant links:

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 links:

CCAR1 (HGNC:):

CCAR1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCAR1	NM_018237.4 linkuse as main transcript	c.1070G>T	p.Arg357Leu	missense_variant	10/25	ENST00000265872.11	NP_060707.2	Q8IX12-1
CCAR1	NM_001282959.2 linkuse as main transcript	c.1025G>T	p.Arg342Leu	missense_variant	9/24		NP_001269888.1	Q8IX12-2
CCAR1	NM_001282960.2 linkuse as main transcript	c.1025G>T	p.Arg342Leu	missense_variant	9/24		NP_001269889.1	Q8IX12-2
CCAR1	NR_104262.2 linkuse as main transcript	n.1170G>T		non_coding_transcript_exon_variant	10/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCAR1	ENST00000265872.11 linkuse as main transcript	c.1070G>T	p.Arg357Leu	missense_variant	10/25	1	NM_018237.4	ENSP00000265872.6		Q8IX12-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.1070G>T (p.R357L) alteration is located in exon 10 (coding exon 9) of the CCAR1 gene. This alteration results from a G to T substitution at nucleotide position 1070, causing the arginine (R) at amino acid position 357 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

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

.;T;.;.;.;.

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

D;D;D;D;D;D

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.65

D;D;D;D;D;D

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.97

.;L;.;.;.;.

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-3.7

.;D;D;D;D;D

REVEL

Uncertain

0.38

Sift

Benign

0.10

.;T;T;T;D;T

Sift4G

Uncertain

0.0070

D;D;D;D;D;D

Polyphen

0.99, 0.99, 1.0

.;D;D;.;D;.

Vest4

0.64

MutPred

0.34

Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);.;.;.;.;

MVP

0.59

MPC

2.0

ClinPred

0.96

GERP RS

5.6

Varity_R

0.37

gMVP

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over