rs1806584

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000353267.8(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
ENST00000353267.8 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.237
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE Protein UniProt
CREB1NM_004379.5 linkuse as main transcriptc.*4488A>G 3_prime_UTR_variant 8/8 ENST00000353267.8 NP_004370.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CREB1ENST00000353267.8 linkuse as main transcriptc.*4488A>G 3_prime_UTR_variant 8/81 NM_004379.5 ENSP00000236995 P1P16220-2

Frequencies

GnomAD3 genomes
AF:
0.127
AC:
19377
AN:
152106
Hom.:
1646
Cov.:
32
show subpopulations
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0367
Gnomad4 AMR exome
AF:
0.111
Gnomad4 ASJ exome
AF:
0.194
Gnomad4 EAS exome
AF:
0.000134
Gnomad4 SAS exome
AF:
0.0784
Gnomad4 FIN exome
AF:
0.278
Gnomad4 NFE exome
AF:
0.182
Gnomad4 OTH exome
AF:
0.131
GnomAD4 genome
AF:
0.127
AC:
19371
AN:
152224
Hom.:
1646
Cov.:
32
AF XY:
0.124
AC XY:
9194
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.0357
Gnomad4 AMR
AF:
0.122
Gnomad4 ASJ
AF:
0.185
Gnomad4 EAS
AF:
0.000964
Gnomad4 SAS
AF:
0.0604
Gnomad4 FIN
AF:
0.139
Gnomad4 NFE
AF:
0.191
Gnomad4 OTH
AF:
0.140
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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1806584; hg19: chr2-208466270; API