Variant 1-153974022-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000368607.8(CREB3L4):c.1145C>T(p.Pro382Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CREB3L4
ENST00000368607.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

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 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=0.13913813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB3L4	NM_001255978.2 linkuse as main transcript	c.1145C>T	p.Pro382Leu	missense_variant	10/10	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.1145C>T	p.Pro382Leu	missense_variant	10/10	1	NM_001255978.2	ENSP00000357596	P1	Q8TEY5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727214

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.1145C>T (p.P382L) alteration is located in exon 10 (coding exon 9) of the CREB3L4 gene. This alteration results from a C to T substitution at nucleotide position 1145, causing the proline (P) at amino acid position 382 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

T;T;T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.70

.;.;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.3

M;M;M;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.7

D;D;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Uncertain

0.012

D;D;D;D

Polyphen

0.45

B;B;B;.

Vest4

0.11

MutPred

0.28

Loss of glycosylation at P382 (P = 0.0445);Loss of glycosylation at P382 (P = 0.0445);Loss of glycosylation at P382 (P = 0.0445);.;

MVP

0.83

MPC

0.10

ClinPred

0.85

GERP RS

4.7

Varity_R

0.079

gMVP

0.34

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over