rs10932201

chr2-207561533-G-Achr2-207561533-G-C

Variant summary

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

The NM_004379.5(CREB1):c.261+1161G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,910 control chromosomes in the GnomAD database, including 12,886 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 0.39 (12886 hom., cov: 31)
• Consequence: CREB1 NM_004379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402

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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB1	NM_004379.5	c.261+1161G>A		intron_variant		ENST00000353267.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB1	ENST00000353267.8	c.261+1161G>A		intron_variant		1	NM_004379.5	P1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58903 AN: 151794 Hom.: 12881 Cov.: 31

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.388 AC: 58915 AN: 151910 Hom.: 12886 Cov.: 31 AF XY: 0.393 AC XY: 29199 AN XY: 74234

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.436

Alfa AF: 0.450 Hom.: 15278

Bravo AF: 0.375

Asia WGS AF: 0.501 AC: 1738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	8.3
Dann	Benign	0.87

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: rs10932201; hg19: chr2-208426257;