7-28570527-C-G

Variant summary

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

The NM_182898.4(CREB5):​c.454C>G​(p.Arg152Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R152C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

CREB5
NM_182898.4 missense

Scores

7
9
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.43
Variant links:
Genes affected
CREB5 (HGNC:16844): (cAMP responsive element binding protein 5) The product of this gene belongs to the CRE (cAMP response element)-binding protein family. Members of this family contain zinc-finger and bZIP DNA-binding domains. The encoded protein specifically binds to CRE as a homodimer or a heterodimer with c-Jun or CRE-BP1, and functions as a CRE-dependent trans-activator. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

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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 rank MANE Protein UniProt
CREB5NM_182898.4 linkc.454C>G p.Arg152Gly missense_variant Exon 5 of 11 ENST00000357727.7 NP_878901.2 Q02930-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CREB5ENST00000357727.7 linkc.454C>G p.Arg152Gly missense_variant Exon 5 of 11 1 NM_182898.4 ENSP00000350359.2 Q02930-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461538
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727042
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Uncertain
26
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.85
.;D;.;.
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.92
.;D;D;D
M_CAP
Benign
0.078
D
MetaRNN
Uncertain
0.69
D;D;D;D
MetaSVM
Uncertain
0.019
D
MutationAssessor
Uncertain
2.3
.;M;.;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Uncertain
-3.0
D;D;D;D
REVEL
Uncertain
0.42
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Benign
0.068
T;T;T;T
Polyphen
0.99
.;D;.;.
Vest4
0.78
MutPred
0.20
.;Gain of loop (P = 0.0502);.;.;
MVP
0.65
MPC
1.1
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.60
gMVP
0.77

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.

Other links and lift over

hg19: chr7-28610145; API