rs2254137

chr2-207579304-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004379.5(CREB1):c.839+1649C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,936 control chromosomes in the GnomAD database, including 25,741 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 0.57 (25741 hom., cov: 32)
• Consequence: CREB1 NM_004379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB1	NM_004379.5	c.839+1649C>A		intron_variant		ENST00000353267.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB1	ENST00000353267.8	c.839+1649C>A		intron_variant		1	NM_004379.5	P1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86377 AN: 151818 Hom.: 25737 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.569 AC: 86413 AN: 151936 Hom.: 25741 Cov.: 32 AF XY: 0.567 AC XY: 42133 AN XY: 74260

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.706

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.654

Gnomad4 OTH AF: 0.617

Alfa AF: 0.646 Hom.: 63649

Bravo AF: 0.556

Asia WGS AF: 0.549 AC: 1907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.1
Dann	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs2254137; hg19: chr2-208444028;