rs2709402

chr2-207556253-C-Achr2-207556253-C-T

Variant summary

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

The NM_004379.5(CREB1):c.114+504C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,062 control chromosomes in the GnomAD database, including 2,027 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 0.16 (2027 hom., cov: 32)
• Consequence: CREB1 NM_004379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB1	NM_004379.5	c.114+504C>A		intron_variant		ENST00000353267.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB1	ENST00000353267.8	c.114+504C>A		intron_variant		1	NM_004379.5	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23653 AN: 151944 Hom.: 2027 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.156 AC: 23655 AN: 152062 Hom.: 2027 Cov.: 32 AF XY: 0.151 AC XY: 11190 AN XY: 74328

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0600

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.155

Alfa AF: 0.0835 Hom.: 141

Bravo AF: 0.152

Asia WGS AF: 0.0380 AC: 131 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.29
Dann	Benign	0.45

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: rs2709402; hg19: chr2-208420977;