chr3-9877127-G-A

Position:

• chr3-9877127-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000336832.7(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. 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 ENST00000336832.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.19

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=0.0031389892).
• BP6: Variant 3-9877127-G-A is Benign according to our data. Variant chr3-9877127-G-A is described in ClinVar as [Benign]. Clinvar id is 128770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-9877127-G-A is described in Lovd as [Benign].
• 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIDEC	NM_001321142.2	c.146C>T	p.Thr49Met	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.146C>T	p.Thr49Met	missense_variant	4/7	1	NM_001321142.2	ENSP00000338642	A1

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

GnomAD3 exomes AF: 0.0213 AC: 3366 AN: 157962 Hom.: 45 AF XY: 0.0217 AC XY: 1805 AN XY: 83240

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 SAS exome AF: 0.00678

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

Gnomad4 AFR exome AF: 0.00521

Gnomad4 AMR exome AF: 0.0209

Gnomad4 ASJ exome AF: 0.0144

Gnomad4 EAS exome AF: 0.0000278

Gnomad4 SAS exome AF: 0.00706

Gnomad4 FIN exome AF: 0.0120

Gnomad4 NFE exome AF: 0.0380

Gnomad4 OTH exome AF: 0.0281

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

Gnomad4 AFR AF: 0.00712

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00849

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0368

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0323 Hom.: 154

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 06, 2013

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

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;D;D;.;D
MetaRNN	Benign	0.0031	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.4	.;M;M;M;.
MutationTaster	Benign	1.0	D;D;N;N;N;N
PrimateAI	Benign	0.36	T
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	T
GERP RS		-0.54
Varity_R		0.11
gMVP		0.41

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