Variant 1-153969038-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001255978.2(CREB3L4):c.283C>T(p.Pro95Ser) variant causes a missense change. The variant allele was found at a frequency of 0.294 in 1,613,738 control chromosomes in the GnomAD database, including 71,770 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.26 ( 5747 hom., cov: 32)

Exomes 𝑓: 0.30 ( 66023 hom. )

Consequence

CREB3L4
NM_001255978.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.60

Variant links:

Genes affected

CREB3L4 (HGNC:18854): (cAMP responsive element binding protein 3 like 4) This gene encodes a CREB (cAMP responsive element binding) protein with a transmembrane domain which localizes it to the ER membrane. The encoded protein is a transcriptional activator which contains a dimerization domain, and this protein may function in a number of processing pathways including protein processing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

CREB3L4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032182932).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB3L4	NM_001255978.2 linkuse as main transcript	c.283C>T	p.Pro95Ser	missense_variant	3/10	ENST00000368607.8	NP_001242907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREB3L4	ENST00000368607.8 linkuse as main transcript	c.283C>T	p.Pro95Ser	missense_variant	3/10	1	NM_001255978.2	ENSP00000357596	P1	Q8TEY5-1

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39628

AN:

151982

Hom.:

5747

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.282

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.296

Gnomad OTH

AF:

0.289

GnomAD3 exomes

AF:

0.314

AC:

78884

AN:

251440

Hom.:

13124

AF XY:

0.315

AC XY:

42860

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.432

Gnomad ASJ exome

AF:

0.316

Gnomad EAS exome

AF:

0.270

Gnomad SAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.332

Gnomad NFE exome

AF:

0.307

Gnomad OTH exome

AF:

0.330

GnomAD4 exome

AF:

0.297

AC:

434702

AN:

1461638

Hom.:

66023

Cov.:

AF XY:

0.299

AC XY:

217403

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.427

Gnomad4 ASJ exome

AF:

0.308

Gnomad4 EAS exome

AF:

0.301

Gnomad4 SAS exome

AF:

0.315

Gnomad4 FIN exome

AF:

0.337

Gnomad4 NFE exome

AF:

0.294

Gnomad4 OTH exome

AF:

0.289

GnomAD4 genome

AF:

0.261

AC:

39643

AN:

152100

Hom.:

5747

Cov.:

AF XY:

0.266

AC XY:

19788

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.383

Gnomad4 ASJ

AF:

0.299

Gnomad4 EAS

AF:

0.283

Gnomad4 SAS

AF:

0.320

Gnomad4 FIN

AF:

0.337

Gnomad4 NFE

AF:

0.296

Gnomad4 OTH

AF:

0.287

Alfa

AF:

0.289

Hom.:

17026

Bravo

AF:

0.261

TwinsUK

AF:

0.300

AC:

1113

ALSPAC

AF:

0.284

AC:

1096

ESP6500AA

AF:

0.123

AC:

544

ESP6500EA

AF:

0.283

AC:

2436

ExAC

AF:

0.308

AC:

37341

Asia WGS

AF:

0.277

AC:

964

AN:

3478

EpiCase

AF:

0.308

EpiControl

AF:

0.317

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

T;T;T;.;T;.;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

T;.;.;T;D;T;T

MetaRNN

Benign

0.0032

T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.5

.;M;M;.;M;.;.

MutationTaster

Benign

0.00037

P;P;P;P;P;P

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-4.1

D;D;D;D;D;D;D

REVEL

Benign

0.12

Sift

Benign

0.053

T;D;D;D;D;D;D

Sift4G

Uncertain

0.051

T;T;T;D;T;T;D

Polyphen

0.99

.;D;D;.;D;.;.

Vest4

0.17, 0.16, 0.43, 0.16, 0.34

MPC

0.23

ClinPred

0.021

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.36

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