rs1860759

Positions:

• chr7-28358841-G-A
• chr7-28358841-G-C

Variant summary

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

The ENST00000396299.6(CREB5):​c.-25+59400G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,000 control chromosomes in the GnomAD database, including 21,028 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 0.52 (21028 hom., cov: 31)
• Consequence: CREB5 ENST00000396299.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

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 (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB5	NM_182899.5	c.-25+59400G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB5	ENST00000396299.6	c.-25+59400G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79573 AN: 151882 Hom.: 21022 Cov.: 31

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.524 AC: 79620 AN: 152000 Hom.: 21028 Cov.: 31 AF XY: 0.527 AC XY: 39115 AN XY: 74288

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.539

Alfa AF: 0.534 Hom.: 43918

Bravo AF: 0.522

Asia WGS AF: 0.608 AC: 2116 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	2.5
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1860759; hg19: chr7-28398460;