2-207543169-G-A

Position:

• chr2-207543169-G-A

Variant summary

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

The NM_004379.5(CREB1):​c.-8-12459G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,984 control chromosomes in the GnomAD database, including 25,218 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 0.56 (25218 hom., cov: 31)
• Consequence: CREB1 NM_004379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB1	NM_004379.5	c.-8-12459G>A		intron_variant		ENST00000353267.8	NP_004370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREB1	ENST00000353267.8	c.-8-12459G>A		intron_variant		1	NM_004379.5	ENSP00000236995	P1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84965 AN: 151866 Hom.: 25215 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.559 AC: 84995 AN: 151984 Hom.: 25218 Cov.: 31 AF XY: 0.560 AC XY: 41607 AN XY: 74248

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.604

Alfa AF: 0.611 Hom.: 13702

Bravo AF: 0.543

Asia WGS AF: 0.548 AC: 1900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.39
DANN	Benign	0.21

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: rs2551640; hg19: chr2-208407893;