rs177582

Variant names:

• chr7-28459204-G-A
• rs177582
• NM_182898.4:c.4-28971G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182898.4(CREB5):​c.4-28971G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 151,996 control chromosomes in the GnomAD database, including 4,504 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4504 hom., cov: 32)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB5	NM_182898.4	c.4-28971G>A		intron_variant	Intron 1 of 10	ENST00000357727.7	NP_878901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB5	ENST00000357727.7	c.4-28971G>A		intron_variant	Intron 1 of 10	1	NM_182898.4	ENSP00000350359.2

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34693 AN: 151878 Hom.: 4492 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0981

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.229 AC: 34736 AN: 151996 Hom.: 4504 Cov.: 32 AF XY: 0.223 AC XY: 16597 AN XY: 74304

African (AFR) AF: 0.358 AC: 14828 AN: 41432

American (AMR) AF: 0.154 AC: 2358 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3460

East Asian (EAS) AF: 0.0981 AC: 507 AN: 5168

South Asian (SAS) AF: 0.196 AC: 942 AN: 4816

European-Finnish (FIN) AF: 0.139 AC: 1470 AN: 10574

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13014 AN: 67952

Other (OTH) AF: 0.235 AC: 497 AN: 2114

Alfa AF: 0.233 Hom.: 706

Bravo AF: 0.235

Asia WGS AF: 0.172 AC: 595 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.45
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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: rs177582; hg19: chr7-28498822;