rs3735019

Variant names:

• chr7-137878052-C-T
• rs3735019
• NM_194071.4:c.*2424G>A

Variant summary

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

The NM_194071.4(CREB3L2):​c.*2424G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 229,260 control chromosomes in the GnomAD database, including 1,298 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 0.076 (1104 hom., cov: 32)
  • Exomes 𝑓: 0.037 (194 hom.)
• Consequence: CREB3L2 NM_194071.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB3L2	NM_194071.4	c.*2424G>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000330387.11	NP_919047.2
CREB3L2	NM_001318246.2	c.*2424G>A		3_prime_UTR_variant	Exon 12 of 12		NP_001305175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB3L2	ENST00000330387	c.*2424G>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_194071.4	ENSP00000329140.6

Frequencies

GnomAD3 genomes AF: 0.0758 AC: 11535 AN: 152134 Hom.: 1098 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0975

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00216

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.0366 AC: 2819 AN: 77008 Hom.: 194 Cov.: 0 AF XY: 0.0336 AC XY: 1192 AN XY: 35474

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.0462

Gnomad4 ASJ exome AF: 0.0149

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.0959

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00216

Gnomad4 OTH exome AF: 0.0409

GnomAD4 genome AF: 0.0760 AC: 11570 AN: 152252 Hom.: 1104 Cov.: 32 AF XY: 0.0766 AC XY: 5702 AN XY: 74462

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.0427

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.0969

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00216

Gnomad4 OTH AF: 0.0629

Alfa AF: 0.0174 Hom.: 181

Bravo AF: 0.0833

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.50

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: rs3735019; hg19: chr7-137562798;