Variant 11-46320708-AG-AGG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 10P and 8B. PVS1PM2BP6_Very_Strong

The NM_052854.4(CREB3L1):c.1525dup variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: not found (cov: 31)

Consequence

CREB3L1
NM_052854.4 splice_acceptor

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.25

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 11, offset of -1, new splice context is: ggcctctcttctctctccAGggg. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 11-46320708-A-AG is Benign according to our data. Variant chr11-46320708-A-AG is described in ClinVar as [Benign]. Clinvar id is 402564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB3L1	NM_052854.4 linkuse as main transcript	c.1525dup		splice_acceptor_variant		ENST00000621158.5	NP_443086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREB3L1	ENST00000621158.5 linkuse as main transcript	c.1525dup		splice_acceptor_variant		1	NM_052854.4	ENSP00000481956	P1	Q96BA8-1
CREB3L1	ENST00000616094.1 linkuse as main transcript	n.1119dup		splice_acceptor_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

1.00

AC:

245281

AN:

245288

Hom.:

122637

AF XY:

1.00

AC XY:

132963

AN XY:

132970

show subpopulations

Gnomad AFR exome

AF:

1.00

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

1.00

Hom.:

6765

Asia WGS

AF:

1.00

AC:

3475

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 11819/111824=99.9% -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 17, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Osteogenesis imperfecta type 16

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over