NM_052854.4:c.103-251C>G

Variant names:

• chr11-46299684-C-G
• rs11038856
• NM_052854.4:c.103-251C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_052854.4(CREB3L1):​c.103-251C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,982 control chromosomes in the GnomAD database, including 28,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.58 (28373 hom., cov: 31)
• Consequence: CREB3L1 NM_052854.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.509
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-46299684-C-G is Benign according to our data. Variant chr11-46299684-C-G is described in ClinVar as Benign. ClinVar VariationId is 1232641.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052854.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB3L1	NM_052854.4	MANE Select	c.103-251C>G		intron	N/A	NP_443086.1	Q96BA8-1
	CREB3L1	NM_001425266.1		c.103-251C>G		intron	N/A	NP_001412195.1
	CREB3L1	NM_001425267.1		c.103-251C>G		intron	N/A	NP_001412196.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB3L1	ENST00000621158.5	TSL:1 MANE Select	c.103-251C>G		intron	N/A	ENSP00000481956.1	Q96BA8-1
	CREB3L1	ENST00000862985.1		c.103-251C>G		intron	N/A	ENSP00000533044.1
	CREB3L1	ENST00000862986.1		c.103-251C>G		intron	N/A	ENSP00000533045.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87504 AN: 151864 Hom.: 28321 Cov.: 31

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.576 AC: 87603 AN: 151982 Hom.: 28373 Cov.: 31 AF XY: 0.565 AC XY: 41953 AN XY: 74266

African (AFR) AF: 0.887 AC: 36826 AN: 41502

American (AMR) AF: 0.411 AC: 6267 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1850 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1283 AN: 5180

South Asian (SAS) AF: 0.486 AC: 2342 AN: 4818

European-Finnish (FIN) AF: 0.365 AC: 3848 AN: 10532

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33346 AN: 67942

Other (OTH) AF: 0.552 AC: 1163 AN: 2106

Alfa AF: 0.337 Hom.: 754

Bravo AF: 0.591

Asia WGS AF: 0.453 AC: 1577 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.63
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11038856; hg19: chr11-46321235;