7-28360554-C-T

Variant names:

• chr7-28360554-C-T
• rs12112050
• ENST00000396299.6:c.-25+61113C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000396299.6(CREB5):​c.-25+61113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,838 control chromosomes in the GnomAD database, including 27,694 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 0.60 (27694 hom., cov: 31)
• Consequence: CREB5 ENST00000396299.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB5	NM_182899.5	c.-25+61113C>T		intron_variant	Intron 1 of 9		NP_878902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB5	ENST00000396299.6	c.-25+61113C>T		intron_variant	Intron 1 of 9	1		ENSP00000379593.2

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90789 AN: 151720 Hom.: 27680 Cov.: 31

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.598 AC: 90841 AN: 151838 Hom.: 27694 Cov.: 31 AF XY: 0.595 AC XY: 44163 AN XY: 74220

African (AFR) AF: 0.484 AC: 20022 AN: 41340

American (AMR) AF: 0.664 AC: 10138 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2246 AN: 3470

East Asian (EAS) AF: 0.540 AC: 2779 AN: 5148

South Asian (SAS) AF: 0.635 AC: 3060 AN: 4816

European-Finnish (FIN) AF: 0.592 AC: 6227 AN: 10526

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44123 AN: 67948

Other (OTH) AF: 0.632 AC: 1335 AN: 2112

Alfa AF: 0.635 Hom.: 23273

Bravo AF: 0.598

Asia WGS AF: 0.571 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.94
DANN	Benign	0.46
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12112050; hg19: chr7-28400173;