3-9877092-A-G

Position:

• chr3-9877092-A-G

Variant summary

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

The ENST00000336832.7(CIDEC):​c.181T>C​(p.Tyr61His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,553,410 control chromosomes in the GnomAD database, including 378 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (53 hom., cov: 32)
  • Exomes 𝑓: 0.0094 (325 hom.)
• Consequence: CIDEC ENST00000336832.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0900

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=0.009500384).
• BP6: Variant 3-9877092-A-G is Benign according to our data. Variant chr3-9877092-A-G is described in ClinVar as [Benign]. Clinvar id is 128771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIDEC	NM_001321142.2	c.181T>C	p.Tyr61His	missense_variant	4/7	ENST00000336832.7	NP_001308071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIDEC	ENST00000336832.7	c.181T>C	p.Tyr61His	missense_variant	4/7	1	NM_001321142.2	ENSP00000338642	A1

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2657 AN: 152180 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.00731

Gnomad SAS AF: 0.0810

Gnomad FIN AF: 0.00697

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00423

Gnomad OTH AF: 0.0182

GnomAD3 exomes AF: 0.0184 AC: 2935 AN: 159410 Hom.: 89 AF XY: 0.0206 AC XY: 1731 AN XY: 83938

Gnomad AFR exome AF: 0.0338

Gnomad AMR exome AF: 0.0171

Gnomad ASJ exome AF: 0.0107

Gnomad EAS exome AF: 0.00571

Gnomad SAS exome AF: 0.0697

Gnomad FIN exome AF: 0.00645

Gnomad NFE exome AF: 0.00459

Gnomad OTH exome AF: 0.0139

GnomAD4 exome AF: 0.00943 AC: 13211 AN: 1401112 Hom.: 325 Cov.: 32 AF XY: 0.0110 AC XY: 7627 AN XY: 691208

Gnomad4 AFR exome AF: 0.0371

Gnomad4 AMR exome AF: 0.0163

Gnomad4 ASJ exome AF: 0.0109

Gnomad4 EAS exome AF: 0.00249

Gnomad4 SAS exome AF: 0.0695

Gnomad4 FIN exome AF: 0.00607

Gnomad4 NFE exome AF: 0.00398

Gnomad4 OTH exome AF: 0.0145

GnomAD4 genome AF: 0.0175 AC: 2667 AN: 152298 Hom.: 53 Cov.: 32 AF XY: 0.0189 AC XY: 1410 AN XY: 74470

Gnomad4 AFR AF: 0.0355

Gnomad4 AMR AF: 0.0204

Gnomad4 ASJ AF: 0.0109

Gnomad4 EAS AF: 0.00733

Gnomad4 SAS AF: 0.0809

Gnomad4 FIN AF: 0.00697

Gnomad4 NFE AF: 0.00423

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.00670 Hom.: 13

Bravo AF: 0.0169

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.0314 AC: 136

ESP6500EA AF: 0.00236 AC: 20

ExAC AF: 0.0109 AC: 1137

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 04, 2013

- -

CIDEC-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.6
DANN	Benign	0.26
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.27	T;T;T;.;T
MetaRNN	Benign	0.0095	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	.;N;N;N;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.88	.;.;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.59	.;.;T;T;T
Sift4G	Benign	0.61	T;T;T;T;T
Polyphen		0.0	.;.;B;.;.
Vest4		0.061
MPC		0.016
ClinPred		0.00029	T
GERP RS		1.3
Varity_R		0.019
gMVP		0.20

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: rs79419480; hg19: chr3-9918776;