11-85663949-C-T

Variant names:

• chr11-85663949-C-T
• rs1192
• NM_001039618.4:c.927G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039618.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREBZF	NM_001039618.4	MANE Select	c.927G>A	p.Pro309Pro	synonymous	Exon 1 of 1	NP_001034707.1
	CREBZF	NR_028024.3		n.1181G>A		non_coding_transcript_exon	Exon 1 of 2
	CREBZF	NR_028025.3		n.1181G>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREBZF	ENST00000527447.2	TSL:6 MANE Select	c.927G>A	p.Pro309Pro	synonymous	Exon 1 of 1	ENSP00000433459.1
	CREBZF	ENST00000490820.2	TSL:1	n.927G>A		non_coding_transcript_exon	Exon 1 of 2	ENSP00000434281.1
	CREBZF	ENST00000850607.1		c.927G>A	p.Pro309Pro	synonymous	Exon 1 of 1	ENSP00000520895.1

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

GnomAD2 exomes AF: 0.160 AC: 39711 AN: 248912 AF XY: 0.157

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

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

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

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: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0926 AC: 6295 AN: 68002

Other (OTH) AF: 0.135 AC: 284 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.0
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)

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