rs2237349

Variant names:

• chr7-28723346-C-T
• rs2237349
• NM_182898.4:c.592-876C>T

Variant summary

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

The NM_182898.4(CREB5):​c.592-876C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 152,060 control chromosomes in the GnomAD database, including 27,938 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 (27938 hom., cov: 33)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842
• Publications: 13 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB5	NM_182898.4	c.592-876C>T		intron_variant	Intron 6 of 10	ENST00000357727.7	NP_878901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB5	ENST00000357727.7	c.592-876C>T		intron_variant	Intron 6 of 10	1	NM_182898.4	ENSP00000350359.2

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91377 AN: 151940 Hom.: 27911 Cov.: 33

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.602 AC: 91468 AN: 152060 Hom.: 27938 Cov.: 33 AF XY: 0.604 AC XY: 44873 AN XY: 74334

African (AFR) AF: 0.635 AC: 26326 AN: 41454

American (AMR) AF: 0.686 AC: 10479 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1806 AN: 3468

East Asian (EAS) AF: 0.238 AC: 1234 AN: 5180

South Asian (SAS) AF: 0.626 AC: 3017 AN: 4818

European-Finnish (FIN) AF: 0.615 AC: 6501 AN: 10572

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39967 AN: 67980

Other (OTH) AF: 0.623 AC: 1310 AN: 2104

Alfa AF: 0.598 Hom.: 34098

Bravo AF: 0.604

Asia WGS AF: 0.481 AC: 1674 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.75
PhyloP100		-0.84
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: rs2237349; hg19: chr7-28762963;