7-28492846-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182898.4(CREB5):c.76-2060G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,500 control chromosomes in the GnomAD database, including 4,634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.23 (4634 hom., cov: 33)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.276

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB5	NM_182898.4	c.76-2060G>T		intron_variant		ENST00000357727.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB5	ENST00000357727.7	c.76-2060G>T		intron_variant		1	NM_182898.4	A1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35126 AN: 151422 Hom.: 4631 Cov.: 33

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.232 AC: 35155 AN: 151500 Hom.: 4634 Cov.: 33 AF XY: 0.229 AC XY: 16941 AN XY: 74026

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.198

Alfa AF: 0.183 Hom.: 4036

Bravo AF: 0.240

Asia WGS AF: 0.192 AC: 666 AN: 3474

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Vascular endothelial growth factor (VEGF) inhibitor response Other:1

association, no assertion criteria provided

case-control

Department of Ophthalmology, College of Medicine, Hanyang University

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.1
Dann	Benign	0.79

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

LitVar

Other links and lift over

dbSNP: rs4722804; hg19: chr7-28532464;