Genetic Variant CREB3L1:c.-354C>G (chr11-46277758-C-G) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.75

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CREB3L1	NM_052854.4 link	c.-354C>G		5_prime_UTR_variant	Exon 1 of 12	ENST00000621158.5	NP_443086.1	Q96BA8-1B2RA75

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB3L1	ENST00000621158 link	c.-354C>G		5_prime_UTR_variant	Exon 1 of 12	1	NM_052854.4	ENSP00000481956.1		Q96BA8-1

Frequencies

GnomAD3 genomes

AF:

0.0556

AC:

8460

AN:

152080

Hom.:

787

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00867

AC XY:

371

AN XY:

42812

show subpopulations

Gnomad4 AFR exome

AF:

0.183

AC:

621

AN:

3396

Gnomad4 AMR exome

AF:

0.0163

AC:

AN:

2398

Gnomad4 ASJ exome

AF:

0.00290

AC:

AN:

4488

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

10682

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

806

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

3422

Gnomad4 NFE exome

AF:

0.000870

AC:

AN:

56332

Gnomad4 Remaining exome

AF:

0.0217

AC:

144

AN:

6628

Heterozygous variant carriers

111

148

185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0557

AC:

8477

AN:

152198

Hom.:

790

Cov.:

AF XY:

0.0542

AC XY:

4031

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.192

AC:

0.191909

AN:

0.191909

Gnomad4 AMR

AF:

0.0230

AC:

0.0230005

AN:

0.0230005

Gnomad4 ASJ

AF:

0.00173

AC:

0.00172911

AN:

0.00172911

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000623

AC:

0.000622665

AN:

0.000622665

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000735

AC:

0.000735446

AN:

0.000735446

Gnomad4 OTH

AF:

0.0435

AC:

0.0435194

AN:

0.0435194

Heterozygous variant carriers

344

688

1031

1375

1719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0423

Hom.:

Bravo

AF:

0.0632

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=299/1

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

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