1-40861583-A-G

Variant names:

• chr1-40861583-A-G
• rs1649376673
• NM_133467.3:c.545T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_133467.3(CITED4):​c.545T>C​(p.Val182Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000464 in 1,293,414 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. V182G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: CITED4 NM_133467.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.98
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133467.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED4	NM_133467.3	MANE Select	c.545T>C	p.Val182Ala	missense	Exon 1 of 1	NP_597724.1	Q96RK1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CITED4	ENST00000372638.4	TSL:6 MANE Select	c.545T>C	p.Val182Ala	missense	Exon 1 of 1	ENSP00000361721.2	Q96RK1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000464 AC: 6 AN: 1293414 Hom.: 0 Cov.: 30 AF XY: 0.00000626 AC XY: 4 AN XY: 638786

African (AFR) AF: 0.00 AC: 0 AN: 25420

American (AMR) AF: 0.00 AC: 0 AN: 25494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21920

East Asian (EAS) AF: 0.00 AC: 0 AN: 26808

South Asian (SAS) AF: 0.00 AC: 0 AN: 72768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4654

European-Non Finnish (NFE) AF: 0.00000581 AC: 6 AN: 1032054

Other (OTH) AF: 0.00 AC: 0 AN: 52596

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Benign	0.83
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.44	T
M_CAP	Pathogenic	0.71	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		8.0
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.29
MutPred		0.56		Gain of relative solvent accessibility (P = 0.005)
MVP		0.53
MPC		1.4
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.42
gMVP		0.40
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs1649376673; hg19: chr1-41327255;