rs1806584

Variant names:

• chr2-207601546-A-G
• rs1806584
• NM_004379.5:c.*4488A>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.*4488A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 199,054 control chromosomes in the GnomAD database, including 2,253 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 0.13 (1646 hom., cov: 32)
  • Exomes 𝑓: 0.14 (607 hom.)
• Consequence: CREB1 NM_004379.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 15 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]

METTL21A (HGNC:30476): (methyltransferase 21A, HSPA lysine) Enables ATPase binding activity; Hsp70 protein binding activity; and protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine methylation. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB1	NM_004379.5	c.*4488A>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000353267.8	NP_004370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB1	ENST00000353267.8	c.*4488A>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_004379.5	ENSP00000236995.3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19377 AN: 152106 Hom.: 1646 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0606

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.140 AC: 6577 AN: 46830 Hom.: 607 Cov.: 0 AF XY: 0.142 AC XY: 3104 AN XY: 21794

African (AFR) AF: 0.0367 AC: 75 AN: 2042

American (AMR) AF: 0.111 AC: 142 AN: 1282

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 577 AN: 2974

East Asian (EAS) AF: 0.000134 AC: 1 AN: 7478

South Asian (SAS) AF: 0.0784 AC: 29 AN: 370

European-Finnish (FIN) AF: 0.278 AC: 10 AN: 36

Middle Eastern (MID) AF: 0.176 AC: 51 AN: 290

European-Non Finnish (NFE) AF: 0.182 AC: 5171 AN: 28394

Other (OTH) AF: 0.131 AC: 521 AN: 3964

GnomAD4 genome AF: 0.127 AC: 19371 AN: 152224 Hom.: 1646 Cov.: 32 AF XY: 0.124 AC XY: 9194 AN XY: 74428

African (AFR) AF: 0.0357 AC: 1483 AN: 41576

American (AMR) AF: 0.122 AC: 1868 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3472

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5188

South Asian (SAS) AF: 0.0604 AC: 292 AN: 4832

European-Finnish (FIN) AF: 0.139 AC: 1473 AN: 10592

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13012 AN: 67950

Other (OTH) AF: 0.140 AC: 295 AN: 2114

Alfa AF: 0.162 Hom.: 290

Bravo AF: 0.120

Asia WGS AF: 0.0330 AC: 115 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.21
DANN	Benign	0.65
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1806584; hg19: chr2-208466270;