rs11765845

chr7-28351523-A-Gchr7-28351523-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000396299.6(CREB5):c.-25+52082A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,046 control chromosomes in the GnomAD database, including 34,183 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 0.66 (34183 hom., cov: 32)
• Consequence: CREB5 ENST00000396299.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB5	NM_182899.5	c.-25+52082A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB5	ENST00000396299.6	c.-25+52082A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100646 AN: 151928 Hom.: 34165 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.662 AC: 100706 AN: 152046 Hom.: 34183 Cov.: 32 AF XY: 0.661 AC XY: 49112 AN XY: 74314

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.691

Alfa AF: 0.716 Hom.: 65721

Bravo AF: 0.659

Asia WGS AF: 0.701 AC: 2439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	11
Dann	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11765845; hg19: chr7-28391142;