ENST00000443115.1:c.253C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 13/16 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
• Publications: 10 publications found

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]

CIDEC Gene-Disease associations (from GenCC):

• CIDEC-related familial partial lipodystrophy

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000308530 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000443115.1. 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
	CIDEC	NM_001321142.2	MANE Select	c.600C>T	p.His200His	synonymous	Exon 7 of 7	NP_001308071.1	Q96AQ7-1
	CIDEC	NM_001199623.2		c.639C>T	p.His213His	synonymous	Exon 6 of 6	NP_001186552.1	A0A0A0MRY9
	CIDEC	NM_001199551.2		c.630C>T	p.His210His	synonymous	Exon 7 of 7	NP_001186480.1	Q96AQ7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIDEC	ENST00000443115.1	TSL:1	c.253C>T	p.Arg85Cys	missense	Exon 3 of 3	ENSP00000411356.1	A0A0C4DG75
	CIDEC	ENST00000336832.7	TSL:1 MANE Select	c.600C>T	p.His200His	synonymous	Exon 7 of 7	ENSP00000338642.2	Q96AQ7-1
	CIDEC	ENST00000383817.5	TSL:1	c.639C>T	p.His213His	synonymous	Exon 6 of 6	ENSP00000373328.2	A0A0A0MRY9

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

GnomAD2 exomes AF: 0.0784 AC: 19703 AN: 251258 AF XY: 0.0790

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 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

African (AFR) AF: 0.0136 AC: 456 AN: 33480

American (AMR) AF: 0.0400 AC: 1787 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0872 AC: 2279 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.0341 AC: 2942 AN: 86254

European-Finnish (FIN) AF: 0.171 AC: 9121 AN: 53352

Middle Eastern (MID) AF: 0.0586 AC: 337 AN: 5750

European-Non Finnish (NFE) AF: 0.102 AC: 113229 AN: 1111942

Other (OTH) AF: 0.0819 AC: 4948 AN: 60390

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

African (AFR) AF: 0.0177 AC: 736 AN: 41596

American (AMR) AF: 0.0544 AC: 832 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0801 AC: 278 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5196

South Asian (SAS) AF: 0.0302 AC: 146 AN: 4834

European-Finnish (FIN) AF: 0.171 AC: 1818 AN: 10604

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6974 AN: 68024

Other (OTH) AF: 0.0756 AC: 160 AN: 2116

Alfa AF: 0.0853 Hom.: 1092

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CIDEC-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
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
PhyloP100		-0.030
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17222536; hg19: chr3-9908935; COSMIC: COSV61062607;