chr2-207579304-C-A

Variant names:

• chr2-207579304-C-A
• rs2254137
• NM_004379.5:c.839+1649C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 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=-0.81).
• 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 rank	MANE	Protein	UniProt
CREB1	NM_004379.5	c.839+1649C>A		intron_variant	Intron 7 of 7	ENST00000353267.8	NP_004370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB1	ENST00000353267.8	c.839+1649C>A		intron_variant	Intron 7 of 7	1	NM_004379.5	ENSP00000236995.3

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

African (AFR) AF: 0.389 AC: 16096 AN: 41426

American (AMR) AF: 0.592 AC: 9037 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2449 AN: 3468

East Asian (EAS) AF: 0.636 AC: 3292 AN: 5178

South Asian (SAS) AF: 0.499 AC: 2405 AN: 4816

European-Finnish (FIN) AF: 0.625 AC: 6556 AN: 10486

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44451 AN: 67980

Other (OTH) AF: 0.617 AC: 1305 AN: 2114

Alfa AF: 0.632 Hom.: 130203

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
PhyloP100		0.54
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: rs2254137; hg19: chr2-208444028; COSMIC: COSV107435610; COSMIC: COSV107435610;