rs2237353

Variant names:

• chr7-28758597-C-A
• rs2237353
• NM_182898.4:c.702+34265C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-28758597-C-A
• chr7-28758597-C-G
• chr7-28758597-C-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.702+34265C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,048 control chromosomes in the GnomAD database, including 34,400 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 0.66 (34400 hom., cov: 32)
• Consequence: CREB5 NM_182898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB5	NM_182898.4	MANE Select	c.702+34265C>A		intron	N/A	NP_878901.2
	CREB5	NM_004904.4		c.681+34265C>A		intron	N/A	NP_004895.2
	CREB5	NM_182899.5		c.603+34265C>A		intron	N/A	NP_878902.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB5	ENST00000357727.7	TSL:1 MANE Select	c.702+34265C>A		intron	N/A	ENSP00000350359.2
	CREB5	ENST00000396300.6	TSL:1	c.681+34265C>A		intron	N/A	ENSP00000379594.2
	CREB5	ENST00000396299.6	TSL:1	c.603+34265C>A		intron	N/A	ENSP00000379593.2

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101007 AN: 151930 Hom.: 34356 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.665 AC: 101109 AN: 152048 Hom.: 34400 Cov.: 32 AF XY: 0.670 AC XY: 49769 AN XY: 74324

African (AFR) AF: 0.502 AC: 20790 AN: 41430

American (AMR) AF: 0.709 AC: 10842 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2532 AN: 3466

East Asian (EAS) AF: 0.735 AC: 3803 AN: 5174

South Asian (SAS) AF: 0.730 AC: 3515 AN: 4812

European-Finnish (FIN) AF: 0.717 AC: 7592 AN: 10582

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49710 AN: 67984

Other (OTH) AF: 0.663 AC: 1400 AN: 2112

Alfa AF: 0.711 Hom.: 28983

Bravo AF: 0.656

Asia WGS AF: 0.732 AC: 2550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.76
PhyloP100		-0.77
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: rs2237353; hg19: chr7-28798214;