11-46277758-C-G

Position:

• chr11-46277758-C-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_052854.4(CREB3L1):​c.-354C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 240,864 control chromosomes in the GnomAD database, including 845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (790 hom., cov: 32)
  • Exomes 𝑓: 0.0099 (55 hom.)
• Consequence: CREB3L1 NM_052854.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.75

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 11-46277758-C-G is Benign according to our data. Variant chr11-46277758-C-G is described in ClinVar as [Benign]. Clinvar id is 1252760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB3L1	NM_052854.4	c.-354C>G		5_prime_UTR_variant	1/12	ENST00000621158.5	NP_443086.1
CREB3L1	XM_006718380.4	c.-354C>G		5_prime_UTR_variant	1/9		XP_006718443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREB3L1	ENST00000621158.5	c.-354C>G		5_prime_UTR_variant	1/12	1	NM_052854.4	ENSP00000481956	P1

Frequencies

GnomAD3 genomes AF: 0.0556 AC: 8460 AN: 152080 Hom.: 787 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.0440

GnomAD4 exome AF: 0.00986 AC: 874 AN: 88666 Hom.: 55 Cov.: 0 AF XY: 0.00867 AC XY: 371 AN XY: 42812

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.0163

Gnomad4 ASJ exome AF: 0.00290

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000870

Gnomad4 OTH exome AF: 0.0217

GnomAD4 genome AF: 0.0557 AC: 8477 AN: 152198 Hom.: 790 Cov.: 32 AF XY: 0.0542 AC XY: 4031 AN XY: 74412

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.0230

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.0435

Alfa AF: 0.0423 Hom.: 55

Bravo AF: 0.0632

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs11038846; hg19: chr11-46299309;