11-46300043-T-C

Variant names:

• chr11-46300043-T-C
• rs561931720
• NM_052854.4:c.211T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_052854.4(CREB3L1):​c.211T>C​(p.Leu71Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CREB3L1 NM_052854.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=1.37 with no splicing effect.

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.211T>C	p.Leu71Leu	synonymous	Exon 2 of 12	NP_443086.1	Q96BA8-1
	CREB3L1	NM_001425266.1		c.211T>C	p.Leu71Leu	synonymous	Exon 2 of 12	NP_001412195.1
	CREB3L1	NM_001425267.1		c.211T>C	p.Leu71Leu	synonymous	Exon 2 of 12	NP_001412196.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB3L1	ENST00000621158.5	TSL:1 MANE Select	c.211T>C	p.Leu71Leu	synonymous	Exon 2 of 12	ENSP00000481956.1	Q96BA8-1
	CREB3L1	ENST00000862985.1		c.211T>C	p.Leu71Leu	synonymous	Exon 2 of 12	ENSP00000533044.1
	CREB3L1	ENST00000862986.1		c.211T>C	p.Leu71Leu	synonymous	Exon 2 of 10	ENSP00000533045.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.0
DANN	Benign	0.59
PhyloP100		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs561931720; hg19: chr11-46321594;