rs17811997

Variant names:

• chr2-207576112-G-C
• rs17811997
• NM_004379.5:c.688+658G>C

Variant summary

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

The NM_004379.5(CREB1):​c.688+658G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0544 in 151,384 control chromosomes in the GnomAD database, including 324 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 0.054 (324 hom., cov: 27)
• Consequence: CREB1 NM_004379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 4 publications found

Genes affected

CREB1 (HGNC:2345): (cAMP responsive element binding protein 1) This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds as a homodimer to the cAMP-responsive element, an octameric palindrome. The protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal stimulation of the cAMP pathway. Alternate splicing of this gene results in several transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB1	NM_004379.5	c.688+658G>C		intron_variant	Intron 6 of 7	ENST00000353267.8	NP_004370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB1	ENST00000353267.8	c.688+658G>C		intron_variant	Intron 6 of 7	1	NM_004379.5	ENSP00000236995.3

Frequencies

GnomAD3 genomes AF: 0.0545 AC: 8246 AN: 151268 Hom.: 323 Cov.: 27

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.0531

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0235

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.0725

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

GnomAD4 genome AF: 0.0544 AC: 8239 AN: 151384 Hom.: 324 Cov.: 27 AF XY: 0.0539 AC XY: 3984 AN XY: 73966

African (AFR) AF: 0.0127 AC: 525 AN: 41346

American (AMR) AF: 0.0531 AC: 806 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.0934 AC: 324 AN: 3470

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5154

South Asian (SAS) AF: 0.0239 AC: 115 AN: 4808

European-Finnish (FIN) AF: 0.101 AC: 1040 AN: 10280

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.0751 AC: 5093 AN: 67858

Other (OTH) AF: 0.0708 AC: 148 AN: 2090

Alfa AF: 0.0614 Hom.: 39

Bravo AF: 0.0508

Asia WGS AF: 0.00896 AC: 31 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.50
PhyloP100		-1.4
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: rs17811997; hg19: chr2-208440836;