7-28525881-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.291+18144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 152,104 control chromosomes in the GnomAD database, including 51,610 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 0.82 (51610 hom., cov: 31)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB5	NM_182898.4	c.291+18144C>T		intron_variant		ENST00000357727.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB5	ENST00000357727.7	c.291+18144C>T		intron_variant		1	NM_182898.4	A1

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125083 AN: 151986 Hom.: 51564 Cov.: 31

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.823 AC: 125178 AN: 152104 Hom.: 51610 Cov.: 31 AF XY: 0.829 AC XY: 61621 AN XY: 74372

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.900

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.810

Alfa AF: 0.831 Hom.: 6540

Bravo AF: 0.819

Asia WGS AF: 0.824 AC: 2868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.6
Dann	Benign	0.70

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: rs150603; hg19: chr7-28565499;