chr11-46320708-AG-A

Variant names:

• chr11-46320708-AG-A
• rs79068197
• NM_052854.4:c.1525delG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_052854.4(CREB3L1):​c.1525delG​(p.Asp509fs) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CREB3L1 NM_052854.4 frameshift, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25
• Publications: 14 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: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0224 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB3L1	NM_052854.4	c.1525delG	p.Asp509fs	frameshift_variant, splice_region_variant	Exon 12 of 12	ENST00000621158.5	NP_443086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB3L1	ENST00000621158.5	c.1524-1delG		splice_acceptor_variant, intron_variant	Intron 11 of 11	1	NM_052854.4	ENSP00000481956.1
CREB3L1	ENST00000616094.1	n.1118-1delG		splice_acceptor_variant, intron_variant	Intron 3 of 3	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2

Splicing

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

Other links and lift over

dbSNP: rs79068197; hg19: chr11-46342259;