7-137915944-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_194071.4(CREB3L2):c.388G>C(p.Val130Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V130I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CREB3L2 NM_194071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025884181).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB3L2	NM_194071.4	c.388G>C	p.Val130Leu	missense_variant	3/12	ENST00000330387.11
CREB3L2	NM_001318246.2	c.199G>C	p.Val67Leu	missense_variant	3/12
CREB3L2	NM_001253775.2	c.388G>C	p.Val130Leu	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB3L2	ENST00000330387.11	c.388G>C	p.Val130Leu	missense_variant	3/12	1	NM_194071.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	5.7
Dann	Benign	0.68
DEOGEN2	Benign	0.057	T;T;.;.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.066	T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.026	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;.;N;N;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.020	N;.;N;N;N;N
REVEL	Benign	0.079
Sift	Benign	0.52	T;.;T;T;T;D
Sift4G	Benign	0.40	T;T;T;T;T;.
Polyphen		0.0	B;.;B;B;.;.
Vest4		0.026
MutPred		0.20		Gain of catalytic residue at V130 (P = 0.0155);Gain of catalytic residue at V130 (P = 0.0155);Gain of catalytic residue at V130 (P = 0.0155);Gain of catalytic residue at V130 (P = 0.0155);.;.;
MVP		0.16
MPC		0.093
ClinPred		0.087	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.050
gMVP		0.021

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: rs273957; hg19: chr7-137600690;