rs61742367

Variant names:

• chr3-9877127-G-A
• rs61742367
• NM_001321142.2:c.146C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-9877127-G-A
• chr3-9877127-G-C
• chr3-9877127-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.19
• Publications: 11 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: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321142.2. 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.146C>T	p.Thr49Met	missense	Exon 4 of 7	NP_001308071.1
	CIDEC	NM_001199623.2		c.185C>T	p.Thr62Met	missense	Exon 3 of 6	NP_001186552.1
	CIDEC	NM_001199551.2		c.146C>T	p.Thr49Met	missense	Exon 3 of 7	NP_001186480.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIDEC	ENST00000336832.7	TSL:1 MANE Select	c.146C>T	p.Thr49Met	missense	Exon 4 of 7	ENSP00000338642.2
	CIDEC	ENST00000383817.5	TSL:1	c.185C>T	p.Thr62Met	missense	Exon 3 of 6	ENSP00000373328.2
	CIDEC	ENST00000443115.1	TSL:1	c.146C>T	p.Thr49Met	missense	Exon 2 of 3	ENSP00000411356.1

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3553 AN: 152190 Hom.: 61 Cov.: 32

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

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.: 32 AF XY: 0.0316 AC XY: 21838 AN XY: 690702

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: 1 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

GnomAD4 genome AF: 0.0233 AC: 3553 AN: 152308 Hom.: 61 Cov.: 32 AF XY: 0.0225 AC XY: 1673 AN XY: 74474

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: 70 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00849 AC: 41 AN: 4828

European-Finnish (FIN) AF: 0.0106 AC: 112 AN: 10612

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0368 AC: 2507 AN: 68034

Other (OTH) AF: 0.0270 AC: 57 AN: 2112

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: 27

ESP6500EA AF: 0.0308 AC: 260

ExAC AF: 0.0109 AC: 1095

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.2
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.13
MPC		0.11
ClinPred		0.026	T
GERP RS		-0.54
Varity_R		0.11
gMVP		0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61742367; hg19: chr3-9918811; COSMIC: COSV61062248; COSMIC: COSV61062248;