rs10233653

chr7-28400701-G-Achr7-28400701-G-C

Variant summary

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

The ENST00000396299.6(CREB5):c.-24-94205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,028 control chromosomes in the GnomAD database, including 8,056 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 0.31 (8056 hom., cov: 32)
• Consequence: CREB5 ENST00000396299.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB5	NM_182899.5	c.-24-94205G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB5	ENST00000396299.6	c.-24-94205G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46496 AN: 151910 Hom.: 8051 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.306 AC: 46507 AN: 152028 Hom.: 8056 Cov.: 32 AF XY: 0.308 AC XY: 22892 AN XY: 74296

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.333

Alfa AF: 0.361 Hom.: 20478

Bravo AF: 0.299

Asia WGS AF: 0.370 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	14
Dann	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10233653; hg19: chr7-28440320;