7-137880527-A-T

Position:

• chr7-137880527-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_194071.4(CREB3L2):​c.1512T>A​(p.Asn504Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CREB3L2 NM_194071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.172

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 Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity CR3L2_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30687755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB3L2	NM_194071.4	c.1512T>A	p.Asn504Lys	missense_variant	12/12	ENST00000330387.11	NP_919047.2
CREB3L2	NM_001318246.2	c.1323T>A	p.Asn441Lys	missense_variant	12/12		NP_001305175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREB3L2	ENST00000330387.11	c.1512T>A	p.Asn504Lys	missense_variant	12/12	1	NM_194071.4	ENSP00000329140.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2024

The c.1512T>A (p.N504K) alteration is located in exon 12 (coding exon 12) of the CREB3L2 gene. This alteration results from a T to A substitution at nucleotide position 1512, causing the asparagine (N) at amino acid position 504 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.20
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.024	D
Polyphen		0.99	D
Vest4		0.44
MutPred		0.25		Gain of solvent accessibility (P = 0.0221);
MVP		0.36
MPC		0.52
ClinPred		0.95	D
GERP RS		-3.6
Varity_R		0.20
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-137565273;