rs273957

Positions:

• chr7-137915944-C-A
• chr7-137915944-C-G
• chr7-137915944-C-T

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>T​(p.Val130Phe) 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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=0.042063564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREB3L2	NM_194071.4	c.388G>T	p.Val130Phe	missense_variant	3/12	ENST00000330387.11	NP_919047.2
CREB3L2	NM_001318246.2	c.199G>T	p.Val67Phe	missense_variant	3/12		NP_001305175.1
CREB3L2	NM_001253775.2	c.388G>T	p.Val130Phe	missense_variant	3/4		NP_001240704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREB3L2	ENST00000330387.11	c.388G>T	p.Val130Phe	missense_variant	3/12	1	NM_194071.4	ENSP00000329140.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461754 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 727174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.92
DEOGEN2	Benign	0.18	T;T;.;.;T;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.22	T;T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.042	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N;.;N;N;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.2	N;.;N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.26	T;.;T;T;T;D
Sift4G	Benign	0.16	T;T;T;T;T;.
Polyphen		0.016	B;.;B;B;.;.
Vest4		0.079
MutPred		0.13		Gain of catalytic residue at V130 (P = 0.1305);Gain of catalytic residue at V130 (P = 0.1305);Gain of catalytic residue at V130 (P = 0.1305);Gain of catalytic residue at V130 (P = 0.1305);.;.;
MVP		0.23
MPC		0.13
ClinPred		0.079	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.069
gMVP		0.036

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;