NM_194071.4:c.388G>A

Variant names:

• chr7-137915944-C-T
• rs273957
• NM_194071.4:c.388G>A

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 50 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
CREB3L2	NM_194071.4	c.388G>A	p.Val130Ile	missense_variant	Exon 3 of 12	ENST00000330387.11	NP_919047.2
CREB3L2	NM_001318246.2	c.199G>A	p.Val67Ile	missense_variant	Exon 3 of 12		NP_001305175.1
CREB3L2	NM_001253775.2	c.388G>A	p.Val130Ile	missense_variant	Exon 3 of 4		NP_001240704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB3L2	ENST00000330387.11	c.388G>A	p.Val130Ile	missense_variant	Exon 3 of 12	1	NM_194071.4	ENSP00000329140.6

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

GnomAD2 exomes AF: 0.686 AC: 172219 AN: 251122 AF XY: 0.673

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 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

African (AFR) AF: 0.935 AC: 31284 AN: 33468

American (AMR) AF: 0.777 AC: 34711 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 16893 AN: 26116

East Asian (EAS) AF: 0.909 AC: 36086 AN: 39694

South Asian (SAS) AF: 0.678 AC: 58412 AN: 86214

European-Finnish (FIN) AF: 0.592 AC: 31623 AN: 53404

Middle Eastern (MID) AF: 0.610 AC: 3515 AN: 5762

European-Non Finnish (NFE) AF: 0.613 AC: 680879 AN: 1111384

Other (OTH) AF: 0.658 AC: 39721 AN: 60378

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

African (AFR) AF: 0.922 AC: 38291 AN: 41538

American (AMR) AF: 0.716 AC: 10929 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2273 AN: 3470

East Asian (EAS) AF: 0.917 AC: 4737 AN: 5166

South Asian (SAS) AF: 0.699 AC: 3355 AN: 4802

European-Finnish (FIN) AF: 0.579 AC: 6105 AN: 10548

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41301 AN: 67966

Other (OTH) AF: 0.689 AC: 1451 AN: 2106

Alfa AF: 0.650 Hom.: 115874

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;.;.
PhyloP100		0.33
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
Mutation Taster		=100/0	polymorphism (auto)

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: rs273957; hg19: chr7-137600690; COSMIC: COSV107362072;