rs273954

Variant names:

• chr7-137918800-A-C
• rs273954
• NM_194071.4:c.320-2788T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194071.4(CREB3L2):​c.320-2788T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,982 control chromosomes in the GnomAD database, including 27,921 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 0.60 (27921 hom., cov: 31)
• Consequence: CREB3L2 NM_194071.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 6 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB3L2	NM_194071.4	c.320-2788T>G		intron_variant	Intron 2 of 11	ENST00000330387.11	NP_919047.2
CREB3L2	NM_001318246.2	c.131-2788T>G		intron_variant	Intron 2 of 11		NP_001305175.1
CREB3L2	NM_001253775.2	c.320-2788T>G		intron_variant	Intron 2 of 3		NP_001240704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB3L2	ENST00000330387.11	c.320-2788T>G		intron_variant	Intron 2 of 11	1	NM_194071.4	ENSP00000329140.6

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91629 AN: 151864 Hom.: 27890 Cov.: 31

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.603 AC: 91720 AN: 151982 Hom.: 27921 Cov.: 31 AF XY: 0.608 AC XY: 45141 AN XY: 74282

African (AFR) AF: 0.550 AC: 22796 AN: 41448

American (AMR) AF: 0.654 AC: 9995 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2240 AN: 3468

East Asian (EAS) AF: 0.901 AC: 4651 AN: 5162

South Asian (SAS) AF: 0.687 AC: 3306 AN: 4814

European-Finnish (FIN) AF: 0.582 AC: 6132 AN: 10540

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40661 AN: 67960

Other (OTH) AF: 0.596 AC: 1258 AN: 2112

Alfa AF: 0.596 Hom.: 4577

Bravo AF: 0.608

Asia WGS AF: 0.762 AC: 2651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.75
PhyloP100		-0.030
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs273954; hg19: chr7-137603546;