ENST00000443115.1:c.253C>T

Variant names:

• chr3-9867251-G-A
• rs17222536
• ENST00000443115.1:c.253C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000443115.1(CIDEC):​c.253C>T​(p.Arg85Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 1,614,072 control chromosomes in the GnomAD database, including 7,757 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (581 hom., cov: 33)
  • Exomes 𝑓: 0.092 (7176 hom.)
• Consequence: CIDEC ENST00000443115.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0300

Genes affected

CIDEC (HGNC:24229): (cell death inducing DFFA like effector c) This gene encodes a member of the cell death-inducing DNA fragmentation factor-like effector family. Members of this family play important roles in apoptosis. The encoded protein promotes lipid droplet formation in adipocytes and may mediate adipocyte apoptosis. This gene is regulated by insulin and its expression is positively correlated with insulin sensitivity. Mutations in this gene may contribute to insulin resistant diabetes. A pseudogene of this gene is located on the short arm of chromosome 3. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015783012).
• BP6: Variant 3-9867251-G-A is Benign according to our data. Variant chr3-9867251-G-A is described in ClinVar as [Benign]. Clinvar id is 128773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIDEC	NM_001321142.2	c.600C>T	p.His200His	synonymous_variant	Exon 7 of 7	ENST00000336832.7	NP_001308071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIDEC	ENST00000336832.7	c.600C>T	p.His200His	synonymous_variant	Exon 7 of 7	1	NM_001321142.2	ENSP00000338642.2

Frequencies

GnomAD3 genomes AF: 0.0724 AC: 11019 AN: 152228 Hom.: 582 Cov.: 33

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0544

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0302

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0774

GnomAD3 exomes AF: 0.0784 AC: 19703 AN: 251258 Hom.: 1093 AF XY: 0.0790 AC XY: 10737 AN XY: 135858

Gnomad AFR exome AF: 0.0141

Gnomad AMR exome AF: 0.0377

Gnomad ASJ exome AF: 0.0863

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0317

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.0865

GnomAD4 exome AF: 0.0924 AC: 135103 AN: 1461726 Hom.: 7176 Cov.: 34 AF XY: 0.0913 AC XY: 66384 AN XY: 727156

Gnomad4 AFR exome AF: 0.0136

Gnomad4 AMR exome AF: 0.0400

Gnomad4 ASJ exome AF: 0.0872

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0341

Gnomad4 FIN exome AF: 0.171

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.0819

GnomAD4 genome AF: 0.0723 AC: 11015 AN: 152346 Hom.: 581 Cov.: 33 AF XY: 0.0746 AC XY: 5560 AN XY: 74494

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.0544

Gnomad4 ASJ AF: 0.0801

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0302

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0756

Alfa AF: 0.0874 Hom.: 812

Bravo AF: 0.0631

TwinsUK AF: 0.0920 AC: 341

ALSPAC AF: 0.106 AC: 408

ESP6500AA AF: 0.0148 AC: 65

ESP6500EA AF: 0.107 AC: 917

ExAC AF: 0.0784 AC: 9518

Asia WGS AF: 0.0160 AC: 59 AN: 3478

EpiCase AF: 0.100

EpiControl AF: 0.101

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

CIDEC-related disorder Benign:1

Dec 02, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	1.0
DANN	Benign	0.71
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.025
Sift	Pathogenic	0.0	D
Vest4		0.18
ClinPred		0.0094	T
GERP RS		1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17222536; hg19: chr3-9908935; COSMIC: COSV61062607;