1-40861665-G-C

Variant names:

• chr1-40861665-G-C
• rs960289755
• NM_133467.3:c.463C>G

Variant summary

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

The NM_133467.3(CITED4):​c.463C>G​(p.Arg155Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000592 in 1,350,660 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R155C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: CITED4 NM_133467.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CITED4	NM_133467.3	c.463C>G	p.Arg155Gly	missense_variant	Exon 1 of 1	ENST00000372638.4	NP_597724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CITED4	ENST00000372638.4	c.463C>G	p.Arg155Gly	missense_variant	Exon 1 of 1	6	NM_133467.3	ENSP00000361721.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000592 AC: 8 AN: 1350660 Hom.: 0 Cov.: 31 AF XY: 0.00000894 AC XY: 6 AN XY: 670912

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: 0.00000659

Gnomad4 OTH exome AF: 0.0000182

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.463C>G (p.R155G) 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 463, causing the arginine (R) at amino acid position 155 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	0.25
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.90	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.015	D
Polyphen		0.99	D
Vest4		0.29
MVP		0.90
MPC		2.2
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.44
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

Other links and lift over

dbSNP: rs960289755; hg19: chr1-41327337;