chr1-40861865-T-G

Variant names:

• chr1-40861865-T-G
• rs1649388636
• NM_133467.3:c.263A>C

Variant summary

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

The NM_133467.3(CITED4):​c.263A>C​(p.His88Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000945 in 1,058,534 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000094 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CITED4 NM_133467.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21
• 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 10 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.263A>C	p.His88Pro	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.263A>C	p.His88Pro	missense	Exon 1 of 1	ENSP00000361721.2	Q96RK1

Frequencies

GnomAD3 genomes AF: 0.00000679 AC: 1 AN: 147360 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000670

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000945 AC: 10 AN: 1058534 Hom.: 0 Cov.: 31 AF XY: 0.00000982 AC XY: 5 AN XY: 509310

African (AFR) AF: 0.00 AC: 0 AN: 20800

American (AMR) AF: 0.00 AC: 0 AN: 9986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12694

East Asian (EAS) AF: 0.00 AC: 0 AN: 19938

South Asian (SAS) AF: 0.00 AC: 0 AN: 31614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2688

European-Non Finnish (NFE) AF: 0.0000111 AC: 10 AN: 901310

Other (OTH) AF: 0.00 AC: 0 AN: 39994

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000679 AC: 1 AN: 147360 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71844

African (AFR) AF: 0.00 AC: 0 AN: 40472

American (AMR) AF: 0.0000670 AC: 1 AN: 14922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3404

East Asian (EAS) AF: 0.00 AC: 0 AN: 4954

South Asian (SAS) AF: 0.00 AC: 0 AN: 4770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66384

Other (OTH) AF: 0.00 AC: 0 AN: 2044

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	Benign	0.082
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Benign	0.86
DEOGEN2	Benign	0.088	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.34	T
M_CAP	Pathogenic	0.75	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.2
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.15	T
Polyphen		0.0060	B
Vest4		0.61
MutPred		0.42		Gain of loop (P = 0.0312)
MVP		0.35
MPC		1.3
ClinPred		0.71	D
GERP RS		1.4
PromoterAI		0.34	Neutral
Varity_R		0.31
gMVP		0.64
Mutation Taster		=81/19	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: rs1649388636; hg19: chr1-41327537;