rs273981

chr7-137934529-T-C

Variant summary

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

The NM_194071.4(CREB3L2):c.103-6163A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,056 control chromosomes in the GnomAD database, including 16,260 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 0.45 (16260 hom., cov: 33)
• Consequence: CREB3L2 NM_194071.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740

Genes affected

CREB3L2 (HGNC:23720): (cAMP responsive element binding protein 3 like 2) This gene encodes a member of the oasis bZIP transcription factor family. Members of this family can dimerize but form homodimers only. The encoded protein is a transcriptional activator. Translocations between this gene on chromosome 7 and the gene fused in sarcoma on chromosome 16 can be found in some tumors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB3L2	NM_194071.4	c.103-6163A>G		intron_variant		ENST00000330387.11
CREB3L2	NM_001253775.2	c.103-6163A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB3L2	ENST00000330387.11	c.103-6163A>G		intron_variant		1	NM_194071.4	P1
CREB3L2	ENST00000452463.5	c.103-6163A>G		intron_variant		1
CREB3L2	ENST00000456390.5	c.103-6163A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68603 AN: 151938 Hom.: 16255 Cov.: 33

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.451 AC: 68652 AN: 152056 Hom.: 16260 Cov.: 33 AF XY: 0.458 AC XY: 34050 AN XY: 74306

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.441

Alfa AF: 0.472 Hom.: 8882

Bravo AF: 0.437

Asia WGS AF: 0.625 AC: 2172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.8
Dann	Benign	0.63

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: rs273981; hg19: chr7-137619275;