rs374897586

Variant names:

• chr7-28570527-C-T
• rs374897586
• NM_182898.4:c.454C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-28570527-C-T
• chr7-28570527-C-A
• chr7-28570527-C-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_182898.4(CREB5):​c.454C>T​(p.Arg152Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000297 in 1,613,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: CREB5 NM_182898.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.752
• BS2: High AC in GnomAd4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182898.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB5	NM_182898.4	MANE Select	c.454C>T	p.Arg152Cys	missense	Exon 5 of 11	NP_878901.2	Q02930-1
	CREB5	NM_004904.4		c.433C>T	p.Arg145Cys	missense	Exon 5 of 11	NP_004895.2	Q02930-2
	CREB5	NM_182899.5		c.355C>T	p.Arg119Cys	missense	Exon 4 of 10	NP_878902.2	Q02930-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB5	ENST00000357727.7	TSL:1 MANE Select	c.454C>T	p.Arg152Cys	missense	Exon 5 of 11	ENSP00000350359.2	Q02930-1
	CREB5	ENST00000396300.6	TSL:1	c.433C>T	p.Arg145Cys	missense	Exon 5 of 11	ENSP00000379594.2	Q02930-2
	CREB5	ENST00000396299.6	TSL:1	c.355C>T	p.Arg119Cys	missense	Exon 4 of 10	ENSP00000379593.2	Q02930-3

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152162 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000518 AC: 13 AN: 250854 AF XY: 0.0000443

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1461538 Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 17 AN XY: 727042

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.000224 AC: 10 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39696

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111830

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152162 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4 AN XY: 74342

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.000196 AC: 3 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000965 Hom.: 0

Bravo AF: 0.0000869

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000494 AC: 6

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.86	D
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	0.036	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.4
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.80
MVP		0.61
MPC		1.3
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.65
gMVP		0.72
Mutation Taster		=52/48	polymorphism

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

Other links and lift over

dbSNP: rs374897586; hg19: chr7-28610145; COSMIC: COSV108201080; COSMIC: COSV108201080;