7-28772876-A-G

Position:

• chr7-28772876-A-G

Variant summary

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

The NM_182898.4(CREB5):​c.703-31323A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 151,810 control chromosomes in the GnomAD database, including 35,760 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 0.68 (35760 hom., cov: 30)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.825

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB5	NM_182898.4	c.703-31323A>G		intron_variant		ENST00000357727.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB5	ENST00000357727.7	c.703-31323A>G		intron_variant		1	NM_182898.4	A1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103495 AN: 151692 Hom.: 35725 Cov.: 30

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.677

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

GnomAD4 genome AF: 0.682 AC: 103591 AN: 151810 Hom.: 35760 Cov.: 30 AF XY: 0.686 AC XY: 50846 AN XY: 74164

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.681

Alfa AF: 0.720 Hom.: 17924

Bravo AF: 0.675

Asia WGS AF: 0.761 AC: 2650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.35
DANN	Benign	0.64

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: rs10238623; hg19: chr7-28812493;