2-207534205-A-G

Variant names:

• chr2-207534205-A-G
• rs889895
• NM_004379.5:c.-9+4071A>G

Variant summary

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

The NM_004379.5(CREB1):​c.-9+4071A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,206 control chromosomes in the GnomAD database, including 2,100 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 0.16 (2100 hom., cov: 33)
• Consequence: CREB1 NM_004379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB1	NM_004379.5	c.-9+4071A>G		intron_variant	Intron 1 of 7	ENST00000353267.8	NP_004370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB1	ENST00000353267.8	c.-9+4071A>G		intron_variant	Intron 1 of 7	1	NM_004379.5	ENSP00000236995.3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24090 AN: 152088 Hom.: 2100 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.158 AC: 24092 AN: 152206 Hom.: 2100 Cov.: 33 AF XY: 0.153 AC XY: 11421 AN XY: 74420

African (AFR) AF: 0.135 AC: 5589 AN: 41534

American (AMR) AF: 0.135 AC: 2071 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 668 AN: 3468

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0592 AC: 286 AN: 4828

European-Finnish (FIN) AF: 0.154 AC: 1633 AN: 10590

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13204 AN: 67984

Other (OTH) AF: 0.158 AC: 333 AN: 2114

Alfa AF: 0.177 Hom.: 3987

Bravo AF: 0.154

Asia WGS AF: 0.0380 AC: 131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.63
PhyloP100		0.0030
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: rs889895; hg19: chr2-208398929;