chr7-137934529-T-C

Variant names:

• chr7-137934529-T-C
• rs273981
• NM_194071.4:c.103-6163A>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.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
• Publications: 4 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=-0.87).
• 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 rank	MANE	Protein	UniProt
CREB3L2	NM_194071.4	c.103-6163A>G		intron_variant	Intron 1 of 11	ENST00000330387.11	NP_919047.2
CREB3L2	NM_001253775.2	c.103-6163A>G		intron_variant	Intron 1 of 3		NP_001240704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB3L2	ENST00000330387.11	c.103-6163A>G		intron_variant	Intron 1 of 11	1	NM_194071.4	ENSP00000329140.6
CREB3L2	ENST00000452463.5	c.103-6163A>G		intron_variant	Intron 1 of 3	1		ENSP00000410314.1
CREB3L2	ENST00000456390.5	c.103-6163A>G		intron_variant	Intron 1 of 9	2		ENSP00000403550.1

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

African (AFR) AF: 0.335 AC: 13914 AN: 41474

American (AMR) AF: 0.400 AC: 6112 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1580 AN: 3470

East Asian (EAS) AF: 0.784 AC: 4056 AN: 5176

South Asian (SAS) AF: 0.549 AC: 2645 AN: 4820

European-Finnish (FIN) AF: 0.573 AC: 6050 AN: 10566

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32749 AN: 67964

Other (OTH) AF: 0.441 AC: 930 AN: 2108

Alfa AF: 0.471 Hom.: 9772

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
PhyloP100		-0.074
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: rs273981; hg19: chr7-137619275;