rs11904814

Variant names:

• chr2-207562074-T-G
• rs11904814
• NM_004379.5:c.261+1702T>G

Variant summary

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

The NM_004379.5(CREB1):​c.261+1702T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,038 control chromosomes in the GnomAD database, including 7,457 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 (7457 hom., cov: 32)
• Consequence: CREB1 NM_004379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304
• Publications: 18 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB1	NM_004379.5	c.261+1702T>G		intron_variant	Intron 3 of 7	ENST00000353267.8	NP_004370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB1	ENST00000353267.8	c.261+1702T>G		intron_variant	Intron 3 of 7	1	NM_004379.5	ENSP00000236995.3

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46302 AN: 151920 Hom.: 7445 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.305 AC: 46352 AN: 152038 Hom.: 7457 Cov.: 32 AF XY: 0.308 AC XY: 22922 AN XY: 74304

African (AFR) AF: 0.244 AC: 10133 AN: 41486

American (AMR) AF: 0.339 AC: 5180 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3472

East Asian (EAS) AF: 0.359 AC: 1859 AN: 5172

South Asian (SAS) AF: 0.497 AC: 2394 AN: 4816

European-Finnish (FIN) AF: 0.349 AC: 3683 AN: 10552

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21539 AN: 67952

Other (OTH) AF: 0.272 AC: 574 AN: 2108

Alfa AF: 0.317 Hom.: 2161

Bravo AF: 0.304

Asia WGS AF: 0.419 AC: 1463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.4
DANN	Benign	0.74
PhyloP100		0.30
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: rs11904814; hg19: chr2-208426798;