chr7-28488178-T-C

Variant names:

• chr7-28488178-T-C
• NM_182898.4:c.7T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_182898.4(CREB5):​c.7T>C​(p.Tyr3His) 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)
• Consequence: CREB5 NM_182898.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.7T>C	p.Tyr3His	missense	Exon 2 of 11	NP_878901.2	Q02930-1
	CREB5	NM_004904.4		c.-15T>C		5_prime_UTR	Exon 2 of 11	NP_004895.2	Q02930-2
	CREB5	NM_182899.5		c.-24-6728T>C		intron	N/A	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.7T>C	p.Tyr3His	missense	Exon 2 of 11	ENSP00000350359.2	Q02930-1
	CREB5	ENST00000396300.6	TSL:1	c.-15T>C		5_prime_UTR	Exon 2 of 11	ENSP00000379594.2	Q02930-2
	CREB5	ENST00000396299.6	TSL:1	c.-24-6728T>C		intron	N/A	ENSP00000379593.2	Q02930-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Benign	0.23
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.7
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.18		Loss of phosphorylation at Y3 (P = 0.0497)
MVP		0.54
MPC		0.53
ClinPred		0.90	D
GERP RS		6.1
Varity_R		0.49
gMVP		0.46
Mutation Taster		=47/53	disease causing

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

hg19: chr7-28527796;