chr1-40861979-G-T

Variant names:

• chr1-40861979-G-T
• rs1558053456
• NM_133467.3:c.149C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_133467.3(CITED4):​c.149C>A​(p.Pro50Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P50L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CITED4 NM_133467.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2777698).

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.149C>A	p.Pro50Gln	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.149C>A	p.Pro50Gln	missense	Exon 1 of 1	ENSP00000361721.2	Q96RK1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1101206 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 530740

African (AFR) AF: 0.00 AC: 0 AN: 22036

American (AMR) AF: 0.00 AC: 0 AN: 8332

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13776

East Asian (EAS) AF: 0.00 AC: 0 AN: 24024

South Asian (SAS) AF: 0.00 AC: 0 AN: 33446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2874

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 930992

Other (OTH) AF: 0.00 AC: 0 AN: 42968

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.31	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.70
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.055
Sift	Benign	0.052	T
Sift4G	Benign	0.16	T
Polyphen		0.041	B
Vest4		0.13
MutPred		0.52		Loss of methylation at R45 (P = 0.087)
MVP		0.60
MPC		1.9
ClinPred		0.17	T
GERP RS		0.56
PromoterAI		-0.036	Neutral
Varity_R		0.034
gMVP		0.41
Mutation Taster		=92/8	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: rs1558053456; hg19: chr1-41327651;