12-12620587-A-G

Position:

• chr12-12620587-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001310.4(CREBL2):​c.15+8400A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,068 control chromosomes in the GnomAD database, including 8,287 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 0.32 (8287 hom., cov: 32)
• Consequence: CREBL2 NM_001310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREBL2	NM_001310.4	c.15+8400A>G		intron_variant		ENST00000228865.3	NP_001301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREBL2	ENST00000228865.3	c.15+8400A>G		intron_variant		1	NM_001310.4	ENSP00000228865	P1
CREBL2	ENST00000540224.1	n.361+8400A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49402 AN: 151950 Hom.: 8286 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.325 AC: 49421 AN: 152068 Hom.: 8287 Cov.: 32 AF XY: 0.320 AC XY: 23801 AN XY: 74336

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.353

Alfa AF: 0.324 Hom.: 4856

Bravo AF: 0.342

Asia WGS AF: 0.362 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.5
DANN	Benign	0.67

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: rs12822507; hg19: chr12-12773521;