7-28627019-A-G

Variant names:

• chr7-28627019-A-G
• rs41295
• NM_182898.4:c.464+56482A>G

Variant summary

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

The NM_182898.4(CREB5):​c.464+56482A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,162 control chromosomes in the GnomAD database, including 31,837 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 0.63 (31837 hom., cov: 33)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB5	NM_182898.4	c.464+56482A>G		intron_variant	Intron 5 of 10	ENST00000357727.7	NP_878901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB5	ENST00000357727.7	c.464+56482A>G		intron_variant	Intron 5 of 10	1	NM_182898.4	ENSP00000350359.2

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96461 AN: 152044 Hom.: 31778 Cov.: 33

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.635 AC: 96574 AN: 152162 Hom.: 31837 Cov.: 33 AF XY: 0.636 AC XY: 47318 AN XY: 74386

African (AFR) AF: 0.762 AC: 31650 AN: 41526

American (AMR) AF: 0.696 AC: 10651 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2145 AN: 3470

East Asian (EAS) AF: 0.900 AC: 4653 AN: 5170

South Asian (SAS) AF: 0.751 AC: 3623 AN: 4822

European-Finnish (FIN) AF: 0.476 AC: 5033 AN: 10568

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.539 AC: 36637 AN: 67996

Other (OTH) AF: 0.637 AC: 1345 AN: 2112

Alfa AF: 0.576 Hom.: 99879

Bravo AF: 0.657

Asia WGS AF: 0.811 AC: 2816 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41295; hg19: chr7-28666636;