Variant 7-137901383-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_194071.4(CREB3L2):c.1014G>C(p.Lys338Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,456,298 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CREB3L2
NM_194071.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38323265).

BS2

High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB3L2	NM_194071.4 linkuse as main transcript	c.1014G>C	p.Lys338Asn	missense_variant	8/12	ENST00000330387.11	NP_919047.2	Q70SY1-1Q68D60
CREB3L2	NM_001318246.2 linkuse as main transcript	c.825G>C	p.Lys275Asn	missense_variant	8/12		NP_001305175.1	Q68D60

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREB3L2	ENST00000330387.11 linkuse as main transcript	c.1014G>C	p.Lys338Asn	missense_variant	8/12	1	NM_194071.4	ENSP00000329140.6		Q70SY1-1
CREB3L2	ENST00000456390.5 linkuse as main transcript	c.1014G>C	p.Lys338Asn	missense_variant	8/10	2		ENSP00000403550.1		Q70SY1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250706

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135498

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1456298

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

724846

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:

0.0000199

Gnomad4 OTH exome

AF:

0.0000166

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

Nov 20, 2024

The c.1014G>C (p.K338N) alteration is located in exon 8 (coding exon 8) of the CREB3L2 gene. This alteration results from a G to C substitution at nucleotide position 1014, causing the lysine (K) at amino acid position 338 to be replaced by an asparagine (N). 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

Pathogenic

0.86

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;.

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0010

D;D

Sift4G

Benign

0.081

T;T

Polyphen

0.60

P;P

Vest4

0.52

MutPred

0.54

Loss of ubiquitination at K338 (P = 0.0019);Loss of ubiquitination at K338 (P = 0.0019);

MVP

0.61

MPC

0.54

ClinPred

0.94

GERP RS

4.6

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.7

Varity_R

0.77

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over