Variant 10-68736923-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000265872.11(CCAR1):c.121A>G(p.Ile41Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CCAR1
ENST00000265872.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057215422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCAR1	NM_018237.4 linkuse as main transcript	c.121A>G	p.Ile41Val	missense_variant	3/25	ENST00000265872.11	NP_060707.2
CCAR1	NM_001282959.2 linkuse as main transcript	c.121A>G	p.Ile41Val	missense_variant	3/24		NP_001269888.1
CCAR1	NM_001282960.2 linkuse as main transcript	c.121A>G	p.Ile41Val	missense_variant	3/24		NP_001269889.1
CCAR1	NR_104262.2 linkuse as main transcript	n.221A>G		non_coding_transcript_exon_variant	3/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCAR1	ENST00000265872.11 linkuse as main transcript	c.121A>G	p.Ile41Val	missense_variant	3/25	1	NM_018237.4	ENSP00000265872	P1	Q8IX12-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251334

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 24, 2023

The c.121A>G (p.I41V) alteration is located in exon 3 (coding exon 2) of the CCAR1 gene. This alteration results from a A to G substitution at nucleotide position 121, causing the isoleucine (I) at amino acid position 41 to be replaced by a valine (V). 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

0.092

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.025

T;.;T;.;.;.;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

D;D;D;D;D;D;D

M_CAP

Benign

0.0042

MetaRNN

Benign

0.057

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;.;N;.;N;.;.

MutationTaster

Benign

0.60

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.46

N;.;N;N;N;N;N

REVEL

Benign

0.076

Sift

Benign

0.23

T;.;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T

Polyphen

0.012, 0.0020

.;.;B;.;B;.;.

Vest4

0.24, 0.24, 0.23

MutPred

0.16

Gain of phosphorylation at Y42 (P = 0.1095);Gain of phosphorylation at Y42 (P = 0.1095);Gain of phosphorylation at Y42 (P = 0.1095);Gain of phosphorylation at Y42 (P = 0.1095);Gain of phosphorylation at Y42 (P = 0.1095);Gain of phosphorylation at Y42 (P = 0.1095);Gain of phosphorylation at Y42 (P = 0.1095);

MVP

0.24

MPC

0.65

ClinPred

0.29

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.039

gMVP

0.18

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