rs1378804199

Variant names:

• chr1-40861850-G-C
• NM_133467.3:c.278C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-40861850-G-C
• chr1-40861850-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_133467.3(CITED4):​c.278C>G​(p.Ala93Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000998 in 1,001,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. A93E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: CITED4 NM_133467.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34193233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CITED4	NM_133467.3	c.278C>G	p.Ala93Gly	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.278C>G	p.Ala93Gly	missense_variant	Exon 1 of 1	6	NM_133467.3	ENSP00000361721.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.98e-7 AC: 1 AN: 1001936 Hom.: 0 Cov.: 31 AF XY: 0.00000211 AC XY: 1 AN XY: 474782

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: 0.00000115

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.036
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.82	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.9	M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	1.5	N
REVEL	Benign	0.27
Sift	Benign	0.47	T
Sift4G	Benign	0.34	T
Polyphen		0.94	P
Vest4		0.071
MutPred		0.53		Gain of catalytic residue at A93 (P = 0.0057);
MVP		0.32
MPC		1.5
ClinPred		0.52	D
GERP RS		3.7
Varity_R		0.084
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-41327522;