chr18-12277227-C-T

Variant names:

• chr18-12277227-C-T
• rs1568108003
• NM_001279.4:c.617C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001279.4(CIDEA):​c.617C>T​(p.Pro206Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. P206S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CIDEA NM_001279.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0620
• Publications: 0 publications found

Genes affected

CIDEA (HGNC:1976): (cell death inducing DFFA like effector a) This gene encodes the homolog of the mouse protein Cidea that has been shown to activate apoptosis. This activation of apoptosis is inhibited by the DNA fragmentation factor DFF45 but not by caspase inhibitors. Mice that lack functional Cidea have higher metabolic rates, higher lipolysis in brown adipose tissue and higher core body temperatures when subjected to cold. These mice are also resistant to diet-induced obesity and diabetes. This suggests that in mice this gene product plays a role in thermogenesis and lipolysis. Alternatively spliced transcripts have been identified. [provided by RefSeq, Aug 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.104777545).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001279.4. 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
	CIDEA	NM_001279.4	MANE Select	c.617C>T	p.Pro206Leu	missense	Exon 5 of 5	NP_001270.1	O60543
	CIDEA	NM_001318383.2		c.719C>T	p.Pro240Leu	missense	Exon 5 of 5	NP_001305312.1	Q8N5P9
	CIDEA	NR_134607.2		n.1442C>T		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIDEA	ENST00000320477.10	TSL:1 MANE Select	c.617C>T	p.Pro206Leu	missense	Exon 5 of 5	ENSP00000320209.8	O60543
	CIDEA	ENST00000521296.5	TSL:1	n.834C>T		non_coding_transcript_exon	Exon 5 of 5
	CIDEA	ENST00000520620.1	TSL:3	n.629C>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.084
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.6
DANN	Benign	0.97
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.062
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.036
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.037	D
Polyphen		0.52	P
Vest4		0.087
MutPred		0.23		Loss of glycosylation at P206 (P = 0.0149)
MVP		0.21
MPC		0.069
ClinPred		0.15	T
GERP RS		1.1
Varity_R		0.067
gMVP		0.16
Mutation Taster		=95/5	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: rs1568108003; hg19: chr18-12277226; COSMIC: COSV100255280; COSMIC: COSV100255280;