7-137908331-G-C

Variant names:

• chr7-137908331-G-C
• rs575391409
• NM_194071.4:c.689C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194071.4(CREB3L2):​c.689C>G​(p.Pro230Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000905 in 1,105,380 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P230L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: CREB3L2 NM_194071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.87
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072508186).

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.689C>G	p.Pro230Arg	missense	Exon 5 of 12	NP_919047.2	Q70SY1-1
	CREB3L2	NM_001318246.2		c.500C>G	p.Pro167Arg	missense	Exon 5 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.689C>G	p.Pro230Arg	missense	Exon 5 of 12	ENSP00000329140.6	Q70SY1-1
	CREB3L2	ENST00000898368.1		c.683C>G	p.Pro228Arg	missense	Exon 5 of 12	ENSP00000568427.1
	CREB3L2	ENST00000456390.5	TSL:2	c.689C>G	p.Pro230Arg	missense	Exon 5 of 10	ENSP00000403550.1	Q70SY1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.05e-7 AC: 1 AN: 1105380 Hom.: 0 Cov.: 31 AF XY: 0.00000191 AC XY: 1 AN XY: 523078

African (AFR) AF: 0.00 AC: 0 AN: 23448

American (AMR) AF: 0.00 AC: 0 AN: 8492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14502

East Asian (EAS) AF: 0.00 AC: 0 AN: 27192

South Asian (SAS) AF: 0.00 AC: 0 AN: 21552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4146

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 924362

Other (OTH) AF: 0.0000226 AC: 1 AN: 44232

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Benign	0.85
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.34	N
PhyloP100		3.9
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.087
Sift	Benign	0.30	T
Sift4G	Benign	0.086	T
Polyphen		0.037	B
Vest4		0.14
MutPred		0.26		Gain of MoRF binding (P = 6e-04)
MVP		0.34
MPC		0.12
ClinPred		0.39	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.069
gMVP		0.27
Mutation Taster		=87/13	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: rs575391409; hg19: chr7-137593077;