chr7-28610646-A-G

Variant names:

• chr7-28610646-A-G
• rs41276
• NM_182898.4:c.464+40109A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_182898.4(CREB5):​c.464+40109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,918 control chromosomes in the GnomAD database, including 4,524 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 0.23 (4524 hom., cov: 31)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB5	NM_182898.4	c.464+40109A>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+40109A>G		intron_variant	Intron 5 of 10	1	NM_182898.4	ENSP00000350359.2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34455 AN: 151800 Hom.: 4517 Cov.: 31

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.227 AC: 34506 AN: 151918 Hom.: 4524 Cov.: 31 AF XY: 0.229 AC XY: 16969 AN XY: 74244

African (AFR) AF: 0.336 AC: 13916 AN: 41402

American (AMR) AF: 0.247 AC: 3774 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2112 AN: 5144

South Asian (SAS) AF: 0.261 AC: 1255 AN: 4802

European-Finnish (FIN) AF: 0.146 AC: 1542 AN: 10560

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.151 AC: 10269 AN: 67954

Other (OTH) AF: 0.224 AC: 473 AN: 2112

Alfa AF: 0.170 Hom.: 4199

Bravo AF: 0.239

Asia WGS AF: 0.346 AC: 1201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.76
PhyloP100		1.1
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: rs41276; hg19: chr7-28650263;