11-85663949-C-T

Position:

• chr11-85663949-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CREBZF	NM_001039618.4	c.927G>A	p.Pro309Pro	synonymous_variant	1/1	ENST00000527447.2	NP_001034707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREBZF	ENST00000527447.2	c.927G>A	p.Pro309Pro	synonymous_variant	1/1	6	NM_001039618.4	ENSP00000433459.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19249 AN: 152004 Hom.: 1467 Cov.: 32

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

GnomAD3 exomes AF: 0.160 AC: 39711 AN: 248912 Hom.: 4202 AF XY: 0.157 AC XY: 21186 AN XY: 135252

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 SAS exome AF: 0.259

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.: 34 AF XY: 0.122 AC XY: 89028 AN XY: 727098

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.0852

Gnomad4 EAS exome AF: 0.277

Gnomad4 SAS exome AF: 0.255

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.0974

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.127 AC: 19297 AN: 152122 Hom.: 1482 Cov.: 32 AF XY: 0.133 AC XY: 9868 AN XY: 74366

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.0738

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0926

Gnomad4 OTH AF: 0.135

Alfa AF: 0.102 Hom.: 1156

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
DANN	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1192; hg19: chr11-85374993; COSMIC: COSV52630030; COSMIC: COSV52630030;