7-137908331-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_194071.4(CREB3L2):​c.689C>T​(p.Pro230Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000135 in 1,257,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: CREB3L2 NM_194071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.068621784).
• BS2: High AC in GnomAd4 at 5 AD gene.

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>T	p.Pro230Leu	missense	Exon 5 of 12	NP_919047.2	Q70SY1-1
	CREB3L2	NM_001318246.2		c.500C>T	p.Pro167Leu	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>T	p.Pro230Leu	missense	Exon 5 of 12	ENSP00000329140.6	Q70SY1-1
	CREB3L2	ENST00000898368.1		c.683C>T	p.Pro228Leu	missense	Exon 5 of 12	ENSP00000568427.1
	CREB3L2	ENST00000456390.5	TSL:2	c.689C>T	p.Pro230Leu	missense	Exon 5 of 10	ENSP00000403550.1	Q70SY1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000109 AC: 12 AN: 1105380 Hom.: 0 Cov.: 31 AF XY: 0.00000956 AC XY: 5 AN XY: 523078

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

American (AMR) AF: 0.000589 AC: 5 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: 0.00000649 AC: 6 AN: 924362

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

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74444

African (AFR) AF: 0.00 AC: 0 AN: 41574

American (AMR) AF: 0.000327 AC: 5 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Benign	0.75
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.9
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.10
Sift	Benign	0.47	T
Sift4G	Benign	0.11	T
Polyphen		0.0030	B
Vest4		0.19
MutPred		0.20		Loss of glycosylation at S228 (P = 0.063)
MVP		0.40
MPC		0.10
ClinPred		0.20	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.064
gMVP		0.28
Mutation Taster		=85/15	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;