2-207550617-C-T

Position:

• chr2-207550617-C-T

Variant summary

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

The NM_004379.5(CREB1):​c.-8-5011C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,168 control chromosomes in the GnomAD database, including 61,753 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 0.89 (61753 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: CREB1 NM_004379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

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]

CREB1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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.-8-5011C>T		intron_variant		ENST00000353267.8	NP_004370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREB1	ENST00000353267.8	c.-8-5011C>T		intron_variant		1	NM_004379.5	ENSP00000236995.3

Frequencies

GnomAD3 genomes AF: 0.893 AC: 135716 AN: 152050 Hom.: 61718 Cov.: 31

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.939

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.995

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.899

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: 0.892 AC: 135809 AN: 152168 Hom.: 61753 Cov.: 31 AF XY: 0.895 AC XY: 66551 AN XY: 74396

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.939

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.995

Gnomad4 FIN AF: 0.975

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.900

Alfa AF: 0.940 Hom.: 13715

Bravo AF: 0.882

Asia WGS AF: 0.977 AC: 3397 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.47

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: rs2709360; hg19: chr2-208415341;