Variant chr7-137882587-G-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 NM_194071.4(CREB3L2):c.1312C>A(p.Pro438Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,556 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CREB3L2
NM_194071.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02

Variant links:

Genes affected

CREB3L2 (HGNC:23720): (cAMP responsive element binding protein 3 like 2) This gene encodes a member of the oasis bZIP transcription factor family. Members of this family can dimerize but form homodimers only. The encoded protein is a transcriptional activator. Translocations between this gene on chromosome 7 and the gene fused in sarcoma on chromosome 16 can be found in some tumors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

CREB3L2 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=0.07737982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB3L2	NM_194071.4 linkuse as main transcript	c.1312C>A	p.Pro438Thr	missense_variant	11/12	ENST00000330387.11	NP_919047.2
CREB3L2	NM_001318246.2 linkuse as main transcript	c.1123C>A	p.Pro375Thr	missense_variant	11/12		NP_001305175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREB3L2	ENST00000330387.11 linkuse as main transcript	c.1312C>A	p.Pro438Thr	missense_variant	11/12	1	NM_194071.4	ENSP00000329140	P1	Q70SY1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459556

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725708

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

Apr 06, 2022

The c.1312C>A (p.P438T) alteration is located in exon 11 (coding exon 11) of the CREB3L2 gene. This alteration results from a C to A substitution at nucleotide position 1312, causing the proline (P) at amino acid position 438 to be replaced by a threonine (T). 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

0.065

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.071

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.80

M_CAP

Benign

0.016

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.26

REVEL

Benign

0.045

Sift

Benign

0.25

Sift4G

Benign

0.76

Polyphen

0.0040

Vest4

0.15

MutPred

0.22

Gain of phosphorylation at P438 (P = 0.0041);

MVP

0.29

MPC

0.11

ClinPred

0.11

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.060

gMVP

0.29

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