7-137885100-C-A

Variant names:

• chr7-137885100-C-A
• rs574310470
• NM_194071.4:c.1165G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_194071.4(CREB3L2):​c.1165G>T​(p.Val389Phe) 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 pathogenic 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. V389I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CREB3L2 NM_194071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.782

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.1165G>T	p.Val389Phe	missense	Exon 10 of 12	NP_919047.2	Q70SY1-1
	CREB3L2	NM_001318246.2		c.976G>T	p.Val326Phe	missense	Exon 10 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.1165G>T	p.Val389Phe	missense	Exon 10 of 12	ENSP00000329140.6	Q70SY1-1
	CREB3L2	ENST00000898368.1		c.1159G>T	p.Val387Phe	missense	Exon 10 of 12	ENSP00000568427.1
	CREB3L2	ENST00000456390.5	TSL:2	c.1165G>T	p.Val389Phe	missense	Exon 10 of 10	ENSP00000403550.1	Q70SY1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251292 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.065
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.29
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.012	D
Polyphen		0.98	D
Vest4		0.75
MutPred		0.49		Loss of helix (P = 0.1706)
MVP		0.76
MPC		0.57
ClinPred		0.80	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.28
gMVP		0.51
Mutation Taster		=83/17	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: rs574310470; hg19: chr7-137569846;