18-12262890-G-C

Variant names:

• chr18-12262890-G-C
• rs765367947
• NM_001279.4:c.104G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001279.4(CIDEA):​c.104G>C​(p.Arg35Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R35H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CIDEA NM_001279.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.66
• Publications: 1 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.933

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.104G>C	p.Arg35Pro	missense	Exon 2 of 5	NP_001270.1	O60543
	CIDEA	NM_001318383.2		c.206G>C	p.Arg69Pro	missense	Exon 2 of 5	NP_001305312.1	Q8N5P9
	CIDEA	NR_134607.2		n.662G>C		non_coding_transcript_exon	Exon 2 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIDEA	ENST00000320477.10	TSL:1 MANE Select	c.104G>C	p.Arg35Pro	missense	Exon 2 of 5	ENSP00000320209.8	O60543
	CIDEA	ENST00000521296.5	TSL:1	n.321G>C		non_coding_transcript_exon	Exon 2 of 5
	CIDEA	ENST00000520620.1	TSL:3	n.298G>C		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251464 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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

American (AMR) AF: 0.0000224 AC: 1 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: 53418

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	D
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.013	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.78		Loss of MoRF binding (P = 0.0054)
MVP		0.52
MPC		0.29
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.80
gMVP		0.76
Mutation Taster		=41/59	disease causing

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: rs765367947; hg19: chr18-12262889;