rs4796955

Positions:

• chr18-12262403-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001279.4(CIDEA):​c.39-422T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,040 control chromosomes in the GnomAD database, including 12,219 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (12219 hom., cov: 32)
• Consequence: CIDEA NM_001279.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIDEA	NM_001279.4	c.39-422T>G		intron_variant		ENST00000320477.10	NP_001270.1
CIDEA	NM_001318383.2	c.141-422T>G		intron_variant			NP_001305312.1
CIDEA	NR_134607.2	n.597-422T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIDEA	ENST00000320477.10	c.39-422T>G		intron_variant		1	NM_001279.4	ENSP00000320209	P1
CIDEA	ENST00000521296.5	n.256-422T>G		intron_variant, non_coding_transcript_variant		1
CIDEA	ENST00000522713.5	c.574-422T>G		intron_variant, NMD_transcript_variant		2		ENSP00000429238
CIDEA	ENST00000520620.1	n.233-422T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55841 AN: 151922 Hom.: 12226 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.376

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.367 AC: 55826 AN: 152040 Hom.: 12219 Cov.: 32 AF XY: 0.374 AC XY: 27806 AN XY: 74296

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.376

Alfa AF: 0.435 Hom.: 20665

Bravo AF: 0.345

Asia WGS AF: 0.458 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.31

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

LitVar

Other links and lift over

dbSNP: rs4796955; hg19: chr18-12262402;