7-28570527-C-G

Variant names:

• chr7-28570527-C-G
• NM_182898.4:c.454C>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 𝑓: 6.8e-7 (0 hom.)
• Consequence: CREB5 NM_182898.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.43

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]

ACMG classification

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
CREB5	NM_182898.4	c.454C>G	p.Arg152Gly	missense_variant	Exon 5 of 11	ENST00000357727.7	NP_878901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB5	ENST00000357727.7	c.454C>G	p.Arg152Gly	missense_variant	Exon 5 of 11	1	NM_182898.4	ENSP00000350359.2

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

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;