rs3730276

Positions:

• chr2-207567622-A-G

Variant summary

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

The NM_004379.5(CREB1):​c.362+59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 1,211,500 control chromosomes in the GnomAD database, including 585 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 0.038 (146 hom., cov: 32)
  • Exomes 𝑓: 0.025 (439 hom.)
• Consequence: CREB1 NM_004379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB1	NM_004379.5	c.362+59A>G		intron_variant		ENST00000353267.8	NP_004370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREB1	ENST00000353267.8	c.362+59A>G		intron_variant		1	NM_004379.5	ENSP00000236995	P1

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 5765 AN: 152106 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.0256

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0276

Gnomad OTH AF: 0.0465

GnomAD4 exome AF: 0.0252 AC: 26686 AN: 1059276 Hom.: 439 Cov.: 13 AF XY: 0.0247 AC XY: 13404 AN XY: 543448

Gnomad4 AFR exome AF: 0.0607

Gnomad4 AMR exome AF: 0.0228

Gnomad4 ASJ exome AF: 0.0525

Gnomad4 EAS exome AF: 0.0000548

Gnomad4 SAS exome AF: 0.00439

Gnomad4 FIN exome AF: 0.0240

Gnomad4 NFE exome AF: 0.0263

Gnomad4 OTH exome AF: 0.0307

GnomAD4 genome AF: 0.0379 AC: 5767 AN: 152224 Hom.: 146 Cov.: 32 AF XY: 0.0377 AC XY: 2803 AN XY: 74434

Gnomad4 AFR AF: 0.0624

Gnomad4 AMR AF: 0.0330

Gnomad4 ASJ AF: 0.0631

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0256

Gnomad4 NFE AF: 0.0276

Gnomad4 OTH AF: 0.0461

Alfa AF: 0.0321 Hom.: 28

Bravo AF: 0.0394

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.5
DANN	Benign	0.83

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: rs3730276; hg19: chr2-208432346;