chr7-28819833-A-G

Position:

• chr7-28819833-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.*554A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 151,728 control chromosomes in the GnomAD database, including 54,192 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 0.84 (54181 hom., cov: 28)
  • Exomes 𝑓: 0.82 (11 hom.)
• Consequence: CREB5 NM_182898.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291

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 (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB5	NM_182898.4	c.*554A>G		3_prime_UTR_variant	11/11	ENST00000357727.7	NP_878901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREB5	ENST00000357727.7	c.*554A>G		3_prime_UTR_variant	11/11	1	NM_182898.4	ENSP00000350359	A1
CREB5	ENST00000396298.6	c.*554A>G		3_prime_UTR_variant	7/7	1		ENSP00000379592
CREB5	ENST00000396299.6	c.*554A>G		3_prime_UTR_variant	10/10	1		ENSP00000379593
CREB5	ENST00000396300.6	c.*554A>G		3_prime_UTR_variant	11/11	1		ENSP00000379594	P4

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127165 AN: 151576 Hom.: 54147 Cov.: 28

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.848

GnomAD4 exome AF: 0.824 AC: 28 AN: 34 Hom.: 11 Cov.: 0 AF XY: 0.800 AC XY: 16 AN XY: 20

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.839 AC: 127250 AN: 151694 Hom.: 54181 Cov.: 28 AF XY: 0.835 AC XY: 61913 AN XY: 74118

Gnomad4 AFR AF: 0.945

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.861

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.844

Alfa AF: 0.832 Hom.: 78393

Bravo AF: 0.834

Asia WGS AF: 0.657 AC: 2288 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	0.89
DANN	Benign	0.54

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: rs2190305; hg19: chr7-28859450;