rs12284298

Variant names:

• chr11-46281085-C-T
• rs12284298
• NM_052854.4:c.102+2872C>T

Variant summary

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

The NM_052854.4(CREB3L1):​c.102+2872C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,986 control chromosomes in the GnomAD database, including 23,462 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 0.54 (23462 hom., cov: 31)
• Consequence: CREB3L1 NM_052854.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 2 publications found

Genes affected

CREB3L1 (HGNC:18856): (cAMP responsive element binding protein 3 like 1) The protein encoded by this gene is normally found in the membrane of the endoplasmic reticulum (ER). However, upon stress to the ER, the encoded protein is cleaved and the released cytoplasmic transcription factor domain translocates to the nucleus. There it activates the transcription of target genes by binding to box-B elements. [provided by RefSeq, Jun 2013]

CREB3L1 Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 16

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• osteogenesis imperfecta type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB3L1	NM_052854.4	c.102+2872C>T		intron_variant	Intron 1 of 11	ENST00000621158.5	NP_443086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB3L1	ENST00000621158.5	c.102+2872C>T		intron_variant	Intron 1 of 11	1	NM_052854.4	ENSP00000481956.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82097 AN: 151868 Hom.: 23433 Cov.: 31

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.541 AC: 82186 AN: 151986 Hom.: 23462 Cov.: 31 AF XY: 0.531 AC XY: 39403 AN XY: 74272

African (AFR) AF: 0.726 AC: 30132 AN: 41476

American (AMR) AF: 0.516 AC: 7884 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1767 AN: 3472

East Asian (EAS) AF: 0.247 AC: 1276 AN: 5156

South Asian (SAS) AF: 0.423 AC: 2035 AN: 4814

European-Finnish (FIN) AF: 0.353 AC: 3728 AN: 10570

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33603 AN: 67916

Other (OTH) AF: 0.550 AC: 1161 AN: 2112

Alfa AF: 0.523 Hom.: 2676

Bravo AF: 0.563

Asia WGS AF: 0.388 AC: 1351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.67
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12284298; hg19: chr11-46302636;