rs2709402

Variant names:

• chr2-207556253-C-A
• rs2709402
• NM_004379.5:c.114+504C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-207556253-C-A
• chr2-207556253-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.88).
• 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 rank	MANE	Protein	UniProt
CREB1	NM_004379.5	c.114+504C>A		intron_variant	Intron 2 of 7	ENST00000353267.8	NP_004370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB1	ENST00000353267.8	c.114+504C>A		intron_variant	Intron 2 of 7	1	NM_004379.5	ENSP00000236995.3

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

African (AFR) AF: 0.134 AC: 5546 AN: 41486

American (AMR) AF: 0.133 AC: 2030 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 643 AN: 3466

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5190

South Asian (SAS) AF: 0.0600 AC: 290 AN: 4830

European-Finnish (FIN) AF: 0.139 AC: 1469 AN: 10544

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.192 AC: 13044 AN: 67956

Other (OTH) AF: 0.155 AC: 328 AN: 2112

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
PhyloP100		-0.29
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: rs2709402; hg19: chr2-208420977;