7-137915944-C-G

Variant names:

• chr7-137915944-C-G
• rs273957
• NM_194071.4:c.388G>C

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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: Not reported in ClinVar
• Conservation: PhyloP100: 0.328
• Publications: 50 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: Likely_benign. The variant received -2 ACMG points.

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

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.388G>C	p.Val130Leu	missense	Exon 3 of 12	NP_919047.2	Q70SY1-1
	CREB3L2	NM_001318246.2		c.199G>C	p.Val67Leu	missense	Exon 3 of 12	NP_001305175.1
	CREB3L2	NM_001253775.2		c.388G>C	p.Val130Leu	missense	Exon 3 of 4	NP_001240704.1	Q70SY1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB3L2	ENST00000330387.11	TSL:1 MANE Select	c.388G>C	p.Val130Leu	missense	Exon 3 of 12	ENSP00000329140.6	Q70SY1-1
	CREB3L2	ENST00000452463.5	TSL:1	c.388G>C	p.Val130Leu	missense	Exon 3 of 4	ENSP00000410314.1	Q70SY1-3
	CREB3L2	ENST00000898368.1		c.388G>C	p.Val130Leu	missense	Exon 3 of 12	ENSP00000568427.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.066	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.33
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.079
Sift	Benign	0.52	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.026
MutPred		0.20		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
Mutation Taster		=100/0	polymorphism

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: rs273957; hg19: chr7-137600690;