dbSNP rs2748543: CIDEB:c.-414-638G>T (chr14-24309468-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001393334.1(CIDEB):c.-1052G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,280 control chromosomes in the GnomAD database, including 2,367 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2366 hom., cov: 32)

Exomes 𝑓: 0.082 ( 1 hom. )

Consequence

CIDEB
NM_001393334.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.422

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:

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
CIDEB	NM_001393334.1 link	c.-1052G>T	5_prime_UTR_variant	Exon 2 of 7	NP_001380263.1
CIDEB	NM_001318807.3 link	c.-414-638G>T	intron_variant	Intron 2 of 7	NP_001305736.1	Q9UHD4
CIDEB	NM_001393335.1 link	c.-447-638G>T	intron_variant	Intron 1 of 6	NP_001380264.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
CIDEB	ENST00000258807.5 link	c.-414-638G>T	intron_variant	Intron 1 of 6	1	ENSP00000258807.5	Q9UHD4
LTB4R2	ENST00000528054 link	c.-1104C>A	5_prime_UTR_variant	Exon 1 of 1		ENSP00000432146.1	A0A3Q5ACI7
CIDEB	ENST00000336557.9 link	c.-414-638G>T	intron_variant	Intron 2 of 7	2	ENSP00000337731.5	Q9UHD4
LTB4R2	ENST00000527924.6 link	c.-95-703C>A	intron_variant	Intron 1 of 2	3	ENSP00000436668.2	E9PIC1

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22852

AN:

152052

Hom.:

2365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0413

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.164

GnomAD4 exome

AF:

0.0818

AC:

AN:

110

Hom.:

Cov.:

AF XY:

0.0972

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

Gnomad4 AMR exome

AC:

AN:

Gnomad4 ASJ exome

AC:

AN:

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

Gnomad4 SAS exome

AC:

AN:

Gnomad4 FIN exome

AF:

0.250

AC:

AN:

Gnomad4 NFE exome

AF:

0.0625

AC:

AN:

Gnomad4 Remaining exome

AF:

0.125

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<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:

0.150

AC:

22857

AN:

152170

Hom.:

2366

Cov.:

AF XY:

0.147

AC XY:

10914

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0412

AC:

0.041177

AN:

0.041177

Gnomad4 AMR

AF:

0.274

AC:

0.273917

AN:

0.273917

Gnomad4 ASJ

AF:

0.188

AC:

0.188184

AN:

0.188184

Gnomad4 EAS

AF:

0.00193

AC:

0.00192976

AN:

0.00192976

Gnomad4 SAS

AF:

0.106

AC:

0.105558

AN:

0.105558

Gnomad4 FIN

AF:

0.132

AC:

0.131967

AN:

0.131967

Gnomad4 NFE

AF:

0.205

AC:

0.204633

AN:

0.204633

Gnomad4 OTH

AF:

0.162

AC:

0.162072

AN:

0.162072

Heterozygous variant carriers

958

1916

2874

3832

4790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

244

488

732

976

1220

<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:

0.182

Hom.:

584

Bravo

AF:

0.156

Asia WGS

AF:

0.0560

AC:

193

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.2

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

Splicing

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