rs61742367

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001321142.2(CIDEC):c.146C>T(p.Thr49Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0314 in 1,552,452 control chromosomes in the GnomAD database, including 910 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 61 hom., cov: 32)

Exomes 𝑓: 0.032 ( 849 hom. )

Consequence

CIDEC
NM_001321142.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.19

Publications

11 publications found

Variant links:

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

CIDEC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031389892).

BP6

Variant 3-9877127-G-A is Benign according to our data. Variant chr3-9877127-G-A is described in ClinVar as Benign. ClinVar VariationId is 128770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0233 (3553/152308) while in subpopulation NFE AF = 0.0368 (2507/68034). AF 95% confidence interval is 0.0356. There are 61 homozygotes in GnomAd4. There are 1673 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 61 Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIDEC	NM_001321142.2 link	c.146C>T	p.Thr49Met	missense_variant	Exon 4 of 7	ENST00000336832.7	NP_001308071.1	Q96AQ7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIDEC	ENST00000336832.7 link	c.146C>T	p.Thr49Met	missense_variant	Exon 4 of 7	1	NM_001321142.2	ENSP00000338642.2		Q96AQ7-1

Frequencies

GnomAD3 genomes

AF:

0.0233

AC:

3553

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00714

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.0280

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00849

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0368

Gnomad OTH

AF:

0.0273

GnomAD2 exomes

AF:

0.0213

AC:

3366

AN:

157962

AF XY:

0.0217

show subpopulations

Gnomad AFR exome

AF:

0.00692

Gnomad AMR exome

AF:

0.0189

Gnomad ASJ exome

AF:

0.0132

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0113

Gnomad NFE exome

AF:

0.0368

Gnomad OTH exome

AF:

0.0298

GnomAD4 exome

AF:

0.0323

AC:

45195

AN:

1400144

Hom.:

849

Cov.:

AF XY:

0.0316

AC XY:

21838

AN XY:

690702

show subpopulations

African (AFR)

AF:

0.00521

AC:

165

AN:

31686

American (AMR)

AF:

0.0209

AC:

748

AN:

35770

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

363

AN:

25184

East Asian (EAS)

AF:

0.0000278

AC:

AN:

35972

South Asian (SAS)

AF:

0.00706

AC:

560

AN:

79286

European-Finnish (FIN)

AF:

0.0120

AC:

590

AN:

49352

Middle Eastern (MID)

AF:

0.0187

AC:

104

AN:

5568

European-Non Finnish (NFE)

AF:

0.0380

AC:

41033

AN:

1079276

Other (OTH)

AF:

0.0281

AC:

1631

AN:

58050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

2268

4536

6803

9071

11339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1514

3028

4542

6056

7570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0233

AC:

3553

AN:

152308

Hom.:

Cov.:

AF XY:

0.0225

AC XY:

1673

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00712

AC:

296

AN:

41570

American (AMR)

AF:

0.0280

AC:

428

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00849

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0106

AC:

112

AN:

10612

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0368

AC:

2507

AN:

68034

Other (OTH)

AF:

0.0270

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

188

375

563

750

938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0313

Hom.:

313

Bravo

AF:

0.0245

TwinsUK

AF:

0.0386

AC:

143

ALSPAC

AF:

0.0431

AC:

166

ESP6500AA

AF:

0.00626

AC:

ESP6500EA

AF:

0.0308

AC:

260

ExAC

AF:

0.0109

AC:

1095

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 06, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.96

D;D;D;.;D

MetaRNN

Benign

0.0031

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

.;M;M;M;.

PhyloP100

1.2

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.3

.;.;N;D;D

REVEL

Benign

0.13

Sift

Uncertain

0.0020

.;.;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D;D

Polyphen

1.0

.;.;D;.;.

Vest4

0.13

MPC

0.11

ClinPred

0.026

GERP RS

-0.54

Varity_R

0.11

gMVP

0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over