1-40862075-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_133467.3(CITED4):​c.53C>G​(p.Pro18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 1,322,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CITED4
NM_133467.3 missense

Scores

3
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.501
Variant links:
Genes affected
CITED4 (HGNC:18696): (Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 4) The protein encoded by this intronless gene belongs to the CITED family of transcriptional coactivators that bind to several proteins, including CREB-binding protein (CBP) and p300, via a conserved 32 aa C-terminal motif, and regulate gene transcription. This protein also interacts with transcription factor AP2 (TFAP2), and thus may function as a co-activator for TFAP2. Hypermethylation and transcriptional downregulation of this gene has been observed in oligodendroglial tumors with deletions of chromosomal arms 1p and 19q, and associated with longer recurrence-free and overall survival of patients with oligodendroglial tumors. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.23408711).
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CITED4NM_133467.3 linkc.53C>G p.Pro18Arg missense_variant Exon 1 of 1 ENST00000372638.4 NP_597724.1 Q96RK1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CITED4ENST00000372638.4 linkc.53C>G p.Pro18Arg missense_variant Exon 1 of 1 6 NM_133467.3 ENSP00000361721.2 Q96RK1

Frequencies

GnomAD3 genomes
AF:
0.0000462
AC:
7
AN:
151634
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00637
Gnomad NFE
AF:
0.0000737
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000162
AC:
19
AN:
1170568
Hom.:
0
Cov.:
32
AF XY:
0.0000210
AC XY:
12
AN XY:
571242
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:
0.0000209
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000619
Gnomad4 OTH exome
AF:
0.0000859
GnomAD4 genome
AF:
0.0000461
AC:
7
AN:
151742
Hom.:
0
Cov.:
32
AF XY:
0.0000270
AC XY:
2
AN XY:
74166
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000737
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
Asia WGS
AF:
0.000296
AC:
1
AN:
3398

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 12, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.53C>G (p.P18R) alteration is located in exon 1 (coding exon 1) of the CITED4 gene. This alteration results from a C to G substitution at nucleotide position 53, causing the proline (P) at amino acid position 18 to be replaced by an arginine (R). 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
0.14
BayesDel_addAF
Benign
-0.0062
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0075
T
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.043
N
LIST_S2
Benign
0.51
T
M_CAP
Pathogenic
0.76
D
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-0.81
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.10
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0060
D
Polyphen
0.45
P
Vest4
0.23
MutPred
0.52
Gain of MoRF binding (P = 0.0026);
MVP
0.28
MPC
2.1
ClinPred
0.47
T
GERP RS
2.2
Varity_R
0.24
gMVP
0.44

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.

Other links and lift over

dbSNP: rs866248556; hg19: chr1-41327747; API