Genetic Variant NM_194071.4:c.*2424G>A (chr7-137878052-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_194071.4(CREB3L2):c.*2424G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 229,260 control chromosomes in the GnomAD database, including 1,298 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.076 ( 1104 hom., cov: 32)

Exomes 𝑓: 0.037 ( 194 hom. )

Consequence

CREB3L2
NM_194071.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.139

Publications

4 publications found

Variant links:

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]

CREB3L2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREB3L2	NM_194071.4 link	c.*2424G>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000330387.11	NP_919047.2	Q70SY1-1Q68D60
CREB3L2	NM_001318246.2 link	c.*2424G>A		3_prime_UTR_variant	Exon 12 of 12		NP_001305175.1	Q68D60

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREB3L2	ENST00000330387.11 link	c.*2424G>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_194071.4	ENSP00000329140.6		Q70SY1-1

Frequencies

GnomAD3 genomes

AF:

0.0758

AC:

11535

AN:

152134

Hom.:

1098

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0423

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.0975

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00216

Gnomad OTH

AF:

0.0612

GnomAD4 exome

AF:

0.0366

AC:

2819

AN:

77008

Hom.:

194

Cov.:

AF XY:

0.0336

AC XY:

1192

AN XY:

35474

show subpopulations

African (AFR)

AF:

0.208

AC:

756

AN:

3638

American (AMR)

AF:

0.0462

AC:

109

AN:

2358

Ashkenazi Jewish (ASJ)

AF:

0.0149

AC:

AN:

4894

East Asian (EAS)

AF:

0.134

AC:

1438

AN:

10770

South Asian (SAS)

AF:

0.0959

AC:

AN:

678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.0258

AC:

AN:

466

European-Non Finnish (NFE)

AF:

0.00216

AC:

103

AN:

47718

Other (OTH)

AF:

0.0409

AC:

263

AN:

6428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

129

257

386

514

643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0760

AC:

11570

AN:

152252

Hom.:

1104

Cov.:

AF XY:

0.0766

AC XY:

5702

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.219

AC:

9084

AN:

41518

American (AMR)

AF:

0.0427

AC:

654

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

AN:

3470

East Asian (EAS)

AF:

0.194

AC:

1003

AN:

5178

South Asian (SAS)

AF:

0.0969

AC:

468

AN:

4828

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00216

AC:

147

AN:

68022

Other (OTH)

AF:

0.0629

AC:

133

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

476

952

1429

1905

2381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0267

Hom.:

415

Bravo

AF:

0.0833

Asia WGS

AF:

0.165

AC:

573

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.0

(source)

DANN

Benign

0.50

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over