7-28724292-C-T

Variant names:

• chr7-28724292-C-T
• rs1803211251
• NM_182898.4:c.662C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182898.4(CREB5):​c.662C>T​(p.Ala221Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. A221D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CREB5 NM_182898.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.23
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16859221).

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.662C>T	p.Ala221Val	missense	Exon 7 of 11	NP_878901.2	Q02930-1
	CREB5	NM_004904.4		c.641C>T	p.Ala214Val	missense	Exon 7 of 11	NP_004895.2	Q02930-2
	CREB5	NM_182899.5		c.563C>T	p.Ala188Val	missense	Exon 6 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.662C>T	p.Ala221Val	missense	Exon 7 of 11	ENSP00000350359.2	Q02930-1
	CREB5	ENST00000396300.6	TSL:1	c.641C>T	p.Ala214Val	missense	Exon 7 of 11	ENSP00000379594.2	Q02930-2
	CREB5	ENST00000396299.6	TSL:1	c.563C>T	p.Ala188Val	missense	Exon 6 of 10	ENSP00000379593.2	Q02930-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.089
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
PhyloP100		7.2
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	0.35	T
Polyphen		0.010	B
Vest4		0.35
MutPred		0.15		Loss of relative solvent accessibility (P = 0.0981)
MVP		0.34
MPC		0.95
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.19
gMVP		0.28
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1803211251; hg19: chr7-28763909;