Variant 7-137928179-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_194071.4(CREB3L2):c.290A>G(p.His97Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CREB3L2
NM_194071.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CREB3L2	NM_194071.4 linkuse as main transcript	c.290A>G	p.His97Arg	missense_variant	2/12	ENST00000330387.11
CREB3L2	NM_001318246.2 linkuse as main transcript	c.101A>G	p.His34Arg	missense_variant	2/12
CREB3L2	NM_001253775.2 linkuse as main transcript	c.290A>G	p.His97Arg	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB3L2	ENST00000330387.11 linkuse as main transcript	c.290A>G	p.His97Arg	missense_variant	2/12	1	NM_194071.4	P1	Q70SY1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1433710

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710826

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:

0.00

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

Oct 30, 2023

The c.290A>G (p.H97R) alteration is located in exon 2 (coding exon 2) of the CREB3L2 gene. This alteration results from a A to G substitution at nucleotide position 290, causing the histidine (H) at amino acid position 97 to be replaced by an arginine (R). 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

0.13

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

Cadd

Benign

Dann

Benign

0.83

DEOGEN2

Uncertain

0.53

D;T;T;.;.;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.83

T;T;T;T;D;T

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.50

T;T;T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.3

M;.;.;M;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.7

D;.;.;D;D;D

REVEL

Benign

0.17

Sift

Benign

0.60

T;.;.;T;T;D

Sift4G

Benign

0.41

T;T;D;T;D;D

Polyphen

0.34

B;.;.;P;P;.

Vest4

0.60

MutPred

0.23

Loss of glycosylation at T100 (P = 0.0671);Loss of glycosylation at T100 (P = 0.0671);Loss of glycosylation at T100 (P = 0.0671);Loss of glycosylation at T100 (P = 0.0671);Loss of glycosylation at T100 (P = 0.0671);.;

MVP

0.63

MPC

0.54

ClinPred

0.58

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.31

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