rs217513

Positions:

• chr7-28505257-C-T

Variant summary

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

The NM_182898.4(CREB5):​c.170-2359C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,118 control chromosomes in the GnomAD database, including 7,472 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 0.30 (7472 hom., cov: 33)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.732

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB5	NM_182898.4	c.170-2359C>T		intron_variant		ENST00000357727.7	NP_878901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREB5	ENST00000357727.7	c.170-2359C>T		intron_variant		1	NM_182898.4	ENSP00000350359	A1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44963 AN: 152000 Hom.: 7464 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.296 AC: 44982 AN: 152118 Hom.: 7472 Cov.: 33 AF XY: 0.297 AC XY: 22095 AN XY: 74352

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.324

Alfa AF: 0.352 Hom.: 13247

Bravo AF: 0.284

Asia WGS AF: 0.284 AC: 990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.92

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: rs217513; hg19: chr7-28544875;