NM_004379.5:c.839+1207C>T

Variant names:

• chr2-207578862-C-T
• rs55834243
• NM_004379.5:c.839+1207C>T

Variant summary

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

The NM_004379.5(CREB1):​c.839+1207C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0545 in 152,120 control chromosomes in the GnomAD database, including 312 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 0.054 (312 hom., cov: 32)
• Consequence: CREB1 NM_004379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.687
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB1	NM_004379.5	c.839+1207C>T		intron_variant	Intron 7 of 7	ENST00000353267.8	NP_004370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB1	ENST00000353267.8	c.839+1207C>T		intron_variant	Intron 7 of 7	1	NM_004379.5	ENSP00000236995.3

Frequencies

GnomAD3 genomes AF: 0.0545 AC: 8281 AN: 152002 Hom.: 312 Cov.: 32

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.0529

Gnomad AMR AF: 0.0828

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0276

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0773

Gnomad OTH AF: 0.0436

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

GnomAD4 genome AF: 0.0545 AC: 8284 AN: 152120 Hom.: 312 Cov.: 32 AF XY: 0.0533 AC XY: 3961 AN XY: 74352

African (AFR) AF: 0.0138 AC: 574 AN: 41508

American (AMR) AF: 0.0830 AC: 1269 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0276 AC: 133 AN: 4812

European-Finnish (FIN) AF: 0.0780 AC: 824 AN: 10560

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0772 AC: 5252 AN: 67996

Other (OTH) AF: 0.0436 AC: 92 AN: 2110

Alfa AF: 0.0358 Hom.: 22

Bravo AF: 0.0549

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.69
PhyloP100		0.69
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: rs55834243; hg19: chr2-208443586;