7-137915944-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194071.4(CREB3L2):c.388G>A(p.Val130Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,613,186 control chromosomes in the GnomAD database, including 343,262 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.72 (40700 hom., cov: 32)
  • Exomes 𝑓: 0.64 (302562 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.3396044E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREB3L2	NM_194071.4	c.388G>A	p.Val130Ile	missense_variant	3/12	ENST00000330387.11
CREB3L2	NM_001318246.2	c.199G>A	p.Val67Ile	missense_variant	3/12
CREB3L2	NM_001253775.2	c.388G>A	p.Val130Ile	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREB3L2	ENST00000330387.11	c.388G>A	p.Val130Ile	missense_variant	3/12	1	NM_194071.4	P1

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109061 AN: 151954 Hom.: 40636 Cov.: 32

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.690

GnomAD3 exomes AF: 0.686 AC: 172219 AN: 251122 Hom.: 60859 AF XY: 0.673 AC XY: 91398 AN XY: 135720

Gnomad AFR exome AF: 0.931

Gnomad AMR exome AF: 0.786

Gnomad ASJ exome AF: 0.647

Gnomad EAS exome AF: 0.925

Gnomad SAS exome AF: 0.678

Gnomad FIN exome AF: 0.588

Gnomad NFE exome AF: 0.607

Gnomad OTH exome AF: 0.659

GnomAD4 exome AF: 0.639 AC: 933124 AN: 1461114 Hom.: 302562 Cov.: 40 AF XY: 0.638 AC XY: 463524 AN XY: 726902

Gnomad4 AFR exome AF: 0.935

Gnomad4 AMR exome AF: 0.777

Gnomad4 ASJ exome AF: 0.647

Gnomad4 EAS exome AF: 0.909

Gnomad4 SAS exome AF: 0.678

Gnomad4 FIN exome AF: 0.592

Gnomad4 NFE exome AF: 0.613

Gnomad4 OTH exome AF: 0.658

GnomAD4 genome AF: 0.718 AC: 109188 AN: 152072 Hom.: 40700 Cov.: 32 AF XY: 0.718 AC XY: 53384 AN XY: 74324

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.689

Alfa AF: 0.636 Hom.: 77965

Bravo AF: 0.738

TwinsUK AF: 0.611 AC: 2265

ALSPAC AF: 0.617 AC: 2377

ESP6500AA AF: 0.914 AC: 4026

ESP6500EA AF: 0.613 AC: 5274

ExAC AF: 0.689 AC: 83662

Asia WGS AF: 0.805 AC: 2802 AN: 3478

EpiCase AF: 0.610

EpiControl AF: 0.608

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	7.1
Dann	Benign	0.27
DEOGEN2	Benign	0.074	T;T;.;.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.0083	T;T;T;T;T;T
MetaRNN	Benign	6.3e-7	T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.7	N;.;N;N;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.11	N;.;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	1.0	T;.;T;T;T;T
Sift4G	Benign	0.25	T;T;T;T;T;.
Polyphen		0.0	B;.;B;B;.;.
Vest4		0.0080
MPC		0.077
ClinPred		0.0037	T
GERP RS		5.0
Varity_R		0.033
gMVP		0.015

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;