Genetic Variant CIDEB:p.Val138Leu (chr14-24306062-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001393339.1(CIDEB):c.412G>T(p.Val138Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

CIDEB
NM_001393339.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.27

Variant links:

Genes affected

CIDEB (HGNC:1977): (cell death inducing DFFA like effector b) Enables identical protein binding activity. Involved in activation of cysteine-type endopeptidase activity; positive regulation of cell death; and positive regulation of release of cytochrome c from mitochondria. Acts upstream of or within apoptotic process. Located in cytosol and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CIDEB links:

NOP9 (HGNC:19826): (NOP9 nucleolar protein) Enables RNA binding activity. Predicted to be involved in ribosome biogenesis. Predicted to be part of 90S preribosome and preribosome, small subunit precursor. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

NOP9 links:

LTB4R2 (HGNC:19260): (leukotriene B4 receptor 2) Predicted to enable G protein-coupled peptide receptor activity and leukotriene B4 receptor activity. Predicted to be involved in inflammatory response and neuropeptide signaling pathway. Predicted to act upstream of or within keratinocyte migration and signal transduction. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LTB4R2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13280201).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIDEB	NM_001393339.1 link	c.412G>T	p.Val138Leu	missense_variant	Exon 4 of 5	ENST00000554411.6	NP_001380268.1
NOP9	NM_174913.3 link	c.*967C>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000267425.8	NP_777573.1	Q86U38-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIDEB	ENST00000554411.6 link	c.412G>T	p.Val138Leu	missense_variant	Exon 4 of 5	1	NM_001393339.1	ENSP00000451089.1		Q9UHD4
NOP9	ENST00000267425.8 link	c.*967C>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_174913.3	ENSP00000267425.3		Q86U38-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251482

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000499

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000656

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.0000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.089

T;T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.73

M_CAP

Benign

0.012

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.12

N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

2.2

N;N;N

REVEL

Benign

0.19

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0070

B;B;B

Vest4

0.15

MutPred

0.62

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.57

MPC

0.19

ClinPred

0.20

GERP RS

4.2

Varity_R

0.047

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over