chr7-28482694-T-A

Variant names:

• chr7-28482694-T-A
• rs217518
• NM_182898.4:c.4-5481T>A

Variant summary

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

The NM_182898.4(CREB5):​c.4-5481T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,108 control chromosomes in the GnomAD database, including 7,917 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 0.30 (7917 hom., cov: 33)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66
• Publications: 2 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=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182898.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB5	NM_182898.4	MANE Select	c.4-5481T>A		intron	N/A	NP_878901.2	Q02930-1
	CREB5	NM_004904.4		c.-18-5481T>A		intron	N/A	NP_004895.2	Q02930-2
	CREB5	NM_182899.5		c.-24-12212T>A		intron	N/A	NP_878902.2	Q02930-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB5	ENST00000357727.7	TSL:1 MANE Select	c.4-5481T>A		intron	N/A	ENSP00000350359.2	Q02930-1
	CREB5	ENST00000396300.6	TSL:1	c.-18-5481T>A		intron	N/A	ENSP00000379594.2	Q02930-2
	CREB5	ENST00000396299.6	TSL:1	c.-24-12212T>A		intron	N/A	ENSP00000379593.2	Q02930-3

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46092 AN: 151990 Hom.: 7918 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.303 AC: 46096 AN: 152108 Hom.: 7917 Cov.: 33 AF XY: 0.303 AC XY: 22518 AN XY: 74366

African (AFR) AF: 0.147 AC: 6087 AN: 41512

American (AMR) AF: 0.356 AC: 5444 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1622 AN: 3468

East Asian (EAS) AF: 0.150 AC: 777 AN: 5174

South Asian (SAS) AF: 0.325 AC: 1567 AN: 4822

European-Finnish (FIN) AF: 0.371 AC: 3918 AN: 10568

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25634 AN: 67962

Other (OTH) AF: 0.342 AC: 723 AN: 2112

Alfa AF: 0.328 Hom.: 1058

Bravo AF: 0.293

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.55
PhyloP100		2.7
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: rs217518; hg19: chr7-28522312;