Variant rs773414002 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032607.3(CREB3L3):c.60C>G(p.Ile20Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CREB3L3
NM_032607.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.84

Variant links:

Genes affected

CREB3L3 (HGNC:18855): (cAMP responsive element binding protein 3 like 3) This gene encodes a member of the basic-leucine zipper family and the AMP-dependent transcription factor family. The encoded protein is localized to the endoplasmic reticulum and acts as a transcription factor activated by cyclic AMP stimulation. The encoded protein binds the cyclic AMP response element (CRE) and the box-B element and has been linked to acute inflammatory response, hepatocellular carcinoma, triglyceride metabolism, and hepcidin expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

CREB3L3 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=0.18096164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB3L3	NM_032607.3 link	c.60C>G	p.Ile20Met	missense_variant	Exon 2 of 10	ENST00000078445.7	NP_115996.1	Q68CJ9-1
CREB3L3	NM_001271995.2 link	c.60C>G	p.Ile20Met	missense_variant	Exon 2 of 10		NP_001258924.1	Q68CJ9-2
CREB3L3	NM_001271996.2 link	c.60C>G	p.Ile20Met	missense_variant	Exon 2 of 10		NP_001258925.1	Q68CJ9-4
CREB3L3	NM_001271997.2 link	c.60C>G	p.Ile20Met	missense_variant	Exon 2 of 9		NP_001258926.1	Q68CJ9-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CREB3L3	ENST00000078445.7 link	c.60C>G	p.Ile20Met	missense_variant	Exon 2 of 10	1	NM_032607.3	ENSP00000078445.1	Q68CJ9-1
CREB3L3	ENST00000595923.5 link	c.60C>G	p.Ile20Met	missense_variant	Exon 2 of 10	1		ENSP00000469355.1	Q68CJ9-2
CREB3L3	ENST00000602257.5 link	c.60C>G	p.Ile20Met	missense_variant	Exon 2 of 10	1		ENSP00000472399.1	Q68CJ9-4
CREB3L3	ENST00000602147.1 link	c.60C>G	p.Ile20Met	missense_variant	Exon 2 of 9	1		ENSP00000470119.1	Q68CJ9-5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251172

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135768

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461600

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727106

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.15

DANN

Benign

0.97

DEOGEN2

Benign

0.10

T;.;.;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.54

T;T;T;T

M_CAP

Benign

0.051

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.4

L;L;L;L

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.27

N;.;.;.

REVEL

Benign

0.28

Sift

Benign

0.13

T;.;.;.

Sift4G

Benign

0.069

T;T;T;D

Polyphen

0.14

B;B;.;.

Vest4

0.18

MutPred

0.47

Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);

MVP

0.77

MPC

0.10

ClinPred

0.081

GERP RS

-10

Varity_R

0.041

gMVP

0.11

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