Genetic Variant CREBL2:c.*1940T>C (chr12-12643938-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001310.4(CREBL2):c.*1940T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,554 control chromosomes in the GnomAD database, including 16,727 homozygotes. 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: 𝑓 0.44 ( 16648 hom., cov: 32)

Exomes 𝑓: 0.61 ( 79 hom. )

Consequence

CREBL2
NM_001310.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.768

Publications

12 publications found

Variant links:

Genes affected

CREBL2 (HGNC:2350): (cAMP responsive element binding protein like 2) cAMP response element (CRE)-binding protein-like-2 (CREBL2) was identified in a search to find genes in a commonly deleted region on chromosome 12p13 flanked by ETV6 and CDKN1B genes, frequently associated with hematopoietic malignancies, as well as breast, non-small-cell lung and ovarian cancers. CREBL2 shares a 41% identity with CRE-binding protein (CREB) over a 48-base long region which encodes the bZip domain of CREB. The bZip domain consists of about 30 amino acids rich in basic residues involved in DNA binding, followed by a leucine zipper motif involved in protein dimerization. This suggests that CREBL2 encodes a protein with DNA binding capabilities. The occurance of CREBL2 deletion in malignancy suggests that CREBL2 may act as a tumor suppressor gene. [provided by RefSeq, Jul 2008]

CREBL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREBL2	NM_001310.4 link	c.*1940T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000228865.3	NP_001301.1	O60519

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREBL2	ENST00000228865.3 link	c.*1940T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_001310.4	ENSP00000228865.2		O60519

Frequencies

GnomAD3 genomes

AF:

0.441

AC:

67026

AN:

152002

Hom.:

16647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.619

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.543

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.625

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.437

GnomAD4 exome

AF:

0.611

AC:

264

AN:

432

Hom.:

Cov.:

AF XY:

0.646

AC XY:

168

AN XY:

260

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.613

AC:

261

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.441

AC:

67036

AN:

152122

Hom.:

16648

Cov.:

AF XY:

0.443

AC XY:

32947

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.220

AC:

9128

AN:

41520

American (AMR)

AF:

0.359

AC:

5492

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.543

AC:

1882

AN:

3468

East Asian (EAS)

AF:

0.431

AC:

2232

AN:

5182

South Asian (SAS)

AF:

0.441

AC:

2132

AN:

4830

European-Finnish (FIN)

AF:

0.625

AC:

6596

AN:

10552

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.558

AC:

37957

AN:

67964

Other (OTH)

AF:

0.433

AC:

917

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1741

3482

5222

6963

8704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<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:

0.516

Hom.:

31035

Bravo

AF:

0.409

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.77

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over