rs3735019

Variant names:

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

Variant summary

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194071.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB3L2	NM_194071.4	MANE Select	c.*2424G>A		3_prime_UTR	Exon 12 of 12	NP_919047.2	Q70SY1-1
	CREB3L2	NM_001318246.2		c.*2424G>A		3_prime_UTR	Exon 12 of 12	NP_001305175.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB3L2	ENST00000330387.11	TSL:1 MANE Select	c.*2424G>A		3_prime_UTR	Exon 12 of 12	ENSP00000329140.6	Q70SY1-1
	CREB3L2	ENST00000898368.1		c.*2424G>A		3_prime_UTR	Exon 12 of 12	ENSP00000568427.1

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

African (AFR) AF: 0.208 AC: 756 AN: 3638

American (AMR) AF: 0.0462 AC: 109 AN: 2358

Ashkenazi Jewish (ASJ) AF: 0.0149 AC: 73 AN: 4894

East Asian (EAS) AF: 0.134 AC: 1438 AN: 10770

South Asian (SAS) AF: 0.0959 AC: 65 AN: 678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 58

Middle Eastern (MID) AF: 0.0258 AC: 12 AN: 466

European-Non Finnish (NFE) AF: 0.00216 AC: 103 AN: 47718

Other (OTH) AF: 0.0409 AC: 263 AN: 6428

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

African (AFR) AF: 0.219 AC: 9084 AN: 41518

American (AMR) AF: 0.0427 AC: 654 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 73 AN: 3470

East Asian (EAS) AF: 0.194 AC: 1003 AN: 5178

South Asian (SAS) AF: 0.0969 AC: 468 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00216 AC: 147 AN: 68022

Other (OTH) AF: 0.0629 AC: 133 AN: 2114

Alfa AF: 0.0267 Hom.: 415

Bravo AF: 0.0833

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.50
PhyloP100		-0.14
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3735019;

hg19: chr7-137562798;