2-207564627-T-C

Variant names:

• chr2-207564627-T-C
• rs6740584
• NM_004379.5:c.262-2836T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004379.5(CREB1):​c.262-2836T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,080 control chromosomes in the GnomAD database, including 12,850 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 0.38 (12850 hom., cov: 31)
• Consequence: CREB1 NM_004379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489
• Publications: 33 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB1	NM_004379.5	c.262-2836T>C		intron_variant	Intron 3 of 7	ENST00000353267.8	NP_004370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB1	ENST00000353267.8	c.262-2836T>C		intron_variant	Intron 3 of 7	1	NM_004379.5	ENSP00000236995.3

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57724 AN: 151962 Hom.: 12846 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.380 AC: 57734 AN: 152080 Hom.: 12850 Cov.: 31 AF XY: 0.387 AC XY: 28755 AN XY: 74322

African (AFR) AF: 0.141 AC: 5841 AN: 41546

American (AMR) AF: 0.442 AC: 6742 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1692 AN: 3466

East Asian (EAS) AF: 0.642 AC: 3323 AN: 5176

South Asian (SAS) AF: 0.430 AC: 2070 AN: 4814

European-Finnish (FIN) AF: 0.523 AC: 5505 AN: 10528

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31140 AN: 67968

Other (OTH) AF: 0.428 AC: 904 AN: 2110

Alfa AF: 0.425 Hom.: 26401

Bravo AF: 0.363

Asia WGS AF: 0.500 AC: 1733 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.2
DANN	Benign	0.41
PhyloP100		0.49
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: rs6740584; hg19: chr2-208429351;