Genetic Variant CREBZF:p.Pro309Pro (chr11-85663949-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001039618.4(CREBZF):c.927G>A(p.Pro309Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,613,698 control chromosomes in the GnomAD database, including 14,758 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 0.13 ( 1482 hom., cov: 32)

Exomes 𝑓: 0.12 ( 13276 hom. )

Consequence

CREBZF
NM_001039618.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.406

Publications

17 publications found

Variant links:

Genes affected

CREBZF (HGNC:24905): (CREB/ATF bZIP transcription factor) Enables identical protein binding activity. Involved in negative regulation of gene expression, epigenetic; regulation of transcription, DNA-templated; and response to virus. Located in mitochondrion and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CREBZF links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP7

Synonymous conserved (PhyloP=-0.406 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREBZF	NM_001039618.4 link	c.927G>A	p.Pro309Pro	synonymous_variant	Exon 1 of 1	ENST00000527447.2	NP_001034707.1	Q9NS37

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREBZF	ENST00000527447.2 link	c.927G>A	p.Pro309Pro	synonymous_variant	Exon 1 of 1	6	NM_001039618.4	ENSP00000433459.1		Q9NS37

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19249

AN:

152004

Hom.:

1467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.0738

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0925

Gnomad OTH

AF:

0.132

GnomAD2 exomes

AF:

0.160

AC:

39711

AN:

248912

AF XY:

0.157

show subpopulations

Gnomad AFR exome

AF:

0.127

Gnomad AMR exome

AF:

0.290

Gnomad ASJ exome

AF:

0.0828

Gnomad EAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.0933

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.120

AC:

175056

AN:

1461576

Hom.:

13276

Cov.:

AF XY:

0.122

AC XY:

89028

AN XY:

727098

show subpopulations

African (AFR)

AF:

0.122

AC:

4093

AN:

33480

American (AMR)

AF:

0.285

AC:

12728

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0852

AC:

2227

AN:

26136

East Asian (EAS)

AF:

0.277

AC:

11003

AN:

39700

South Asian (SAS)

AF:

0.255

AC:

21971

AN:

86258

European-Finnish (FIN)

AF:

0.125

AC:

6624

AN:

53120

Middle Eastern (MID)

AF:

0.0983

AC:

567

AN:

5768

European-Non Finnish (NFE)

AF:

0.0974

AC:

108314

AN:

1112002

Other (OTH)

AF:

0.125

AC:

7529

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

9855

19710

29564

39419

49274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.127

AC:

19297

AN:

152122

Hom.:

1482

Cov.:

AF XY:

0.133

AC XY:

9868

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.127

AC:

5289

AN:

41492

American (AMR)

AF:

0.199

AC:

3037

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0738

AC:

256

AN:

3468

East Asian (EAS)

AF:

0.285

AC:

1467

AN:

5150

South Asian (SAS)

AF:

0.272

AC:

1312

AN:

4818

European-Finnish (FIN)

AF:

0.118

AC:

1252

AN:

10596

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0926

AC:

6295

AN:

68002

Other (OTH)

AF:

0.135

AC:

284

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

841

1682

2523

3364

4205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.106

Hom.:

1546

Bravo

AF:

0.135

Asia WGS

AF:

0.292

AC:

1016

AN:

3478

EpiCase

AF:

0.0961

EpiControl

AF:

0.0973

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

9.0

(source)

DANN

Benign

0.95

PhyloP100

-0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

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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11-85663949-C-T

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