2-207550413-A-G

Position:

• chr2-207550413-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.-8-5215A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 150,226 control chromosomes in the GnomAD database, including 59,640 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 0.88 (59640 hom., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: CREB1 NM_004379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB1	NM_004379.5	c.-8-5215A>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.-8-5215A>G		intron_variant		1	NM_004379.5	ENSP00000236995	P1

Frequencies

GnomAD3 genomes AF: 0.879 AC: 132019 AN: 150116 Hom.: 59614 Cov.: 24

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.995

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.891

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.879 AC: 132092 AN: 150226 Hom.: 59640 Cov.: 24 AF XY: 0.882 AC XY: 64615 AN XY: 73290

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.935

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.995

Gnomad4 FIN AF: 0.974

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.892

Alfa AF: 0.945 Hom.: 8893

Bravo AF: 0.866

Asia WGS AF: 0.975 AC: 3389 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.55

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: rs2709359; hg19: chr2-208415137;