rs273937

chr7-137895133-C-T

Variant summary

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

The NM_194071.4(CREB3L2):c.1043+6221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,138 control chromosomes in the GnomAD database, including 27,067 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 0.56 (27067 hom., cov: 33)
• Consequence: CREB3L2 NM_194071.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.962

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB3L2	NM_194071.4	c.1043+6221G>A		intron_variant		ENST00000330387.11
CREB3L2	NM_001318246.2	c.854+6221G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB3L2	ENST00000330387.11	c.1043+6221G>A		intron_variant		1	NM_194071.4	P1
CREB3L2	ENST00000456390.5	c.1043+6221G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85683 AN: 152020 Hom.: 27046 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.660

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.563 AC: 85723 AN: 152138 Hom.: 27067 Cov.: 33 AF XY: 0.570 AC XY: 42381 AN XY: 74384

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.615

Alfa AF: 0.603 Hom.: 3668

Bravo AF: 0.552

Asia WGS AF: 0.588 AC: 2046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.33
Dann	Benign	0.59

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: rs273937; hg19: chr7-137579879;