1-40861959-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_133467.3(CITED4):​c.169C>G​(p.Arg57Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000884 in 1,243,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

CITED4
NM_133467.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.653
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.04329461).
BS2
High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CITED4NM_133467.3 linkc.169C>G p.Arg57Gly 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.169C>G p.Arg57Gly missense_variant Exon 1 of 1 6 NM_133467.3 ENSP00000361721.2 Q96RK1

Frequencies

GnomAD3 genomes
AF:
0.00000665
AC:
1
AN:
150412
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:
0.00
Gnomad NFE
AF:
0.0000149
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000915
AC:
10
AN:
1093444
Hom.:
0
Cov.:
32
AF XY:
0.0000152
AC XY:
8
AN XY:
526278
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:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000665
AC:
1
AN:
150412
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
73424
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:
0.0000149
Gnomad4 OTH
AF:
0.00
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
Dec 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.169C>G (p.R57G) 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 169, causing the arginine (R) at amino acid position 57 to be replaced by a glycine (G). 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
0.068
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
12
DANN
Benign
0.56
DEOGEN2
Benign
0.00057
T
Eigen
Benign
-0.95
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.066
N
LIST_S2
Benign
0.26
T
M_CAP
Benign
0.0084
T
MetaRNN
Benign
0.043
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
0.80
N
REVEL
Benign
0.088
Sift
Benign
0.25
T
Sift4G
Benign
0.40
T
Polyphen
0.0
B
Vest4
0.051
MutPred
0.29
Loss of solvent accessibility (P = 0.0044);
MVP
0.39
MPC
1.1
ClinPred
0.13
T
GERP RS
1.7
Varity_R
0.058
gMVP
0.38

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: rs1323671916; hg19: chr1-41327631; API