NM_001279.4:c.460A>G

Variant names:

• chr18-12274222-A-G
• rs759048349
• NM_001279.4:c.460A>G

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.460A>G​(p.Met154Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. M154I) 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: 6.68
• 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=0.23103872).

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.460A>G	p.Met154Val	missense	Exon 4 of 5	NP_001270.1	O60543
	CIDEA	NM_001318383.2		c.562A>G	p.Met188Val	missense	Exon 4 of 5	NP_001305312.1	Q8N5P9
	CIDEA	NR_134607.2		n.1285A>G		non_coding_transcript_exon	Exon 5 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIDEA	ENST00000320477.10	TSL:1 MANE Select	c.460A>G	p.Met154Val	missense	Exon 4 of 5	ENSP00000320209.8	O60543
	CIDEA	ENST00000521296.5	TSL:1	n.677A>G		non_coding_transcript_exon	Exon 4 of 5
	CIDEA	ENST00000522713.5	TSL:2	n.*659A>G		non_coding_transcript_exon	Exon 5 of 6	ENSP00000429238.1	E5RJ03

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251446 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 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: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000434 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.032
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.7
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.62	N
REVEL	Uncertain	0.32
Sift	Benign	0.60	T
Sift4G	Benign	0.59	T
Polyphen		0.18	B
Vest4		0.13
MutPred		0.26		Gain of sheet (P = 0.1539)
MVP		0.61
MPC		0.086
ClinPred		0.33	T
GERP RS		5.3
Varity_R		0.25
gMVP		0.22
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: rs759048349; hg19: chr18-12274221;