11-85663949-C-G

Variant names:

• chr11-85663949-C-G
• NM_001039618.4:c.927G>C
• CREBZF p.Pro309Pro

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001039618.4(CREBZF):​c.927G>C​(p.Pro309Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CREBZF NM_001039618.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.406 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREBZF	NM_001039618.4	MANE Select	c.927G>C	p.Pro309Pro	synonymous	Exon 1 of 1	NP_001034707.1	Q9NS37
	CREBZF	NR_028024.3		n.1181G>C		non_coding_transcript_exon	Exon 1 of 2
	CREBZF	NR_028025.3		n.1181G>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREBZF	ENST00000527447.2	TSL:6 MANE Select	c.927G>C	p.Pro309Pro	synonymous	Exon 1 of 1	ENSP00000433459.1	Q9NS37
	CREBZF	ENST00000490820.2	TSL:1	n.927G>C		non_coding_transcript_exon	Exon 1 of 2	ENSP00000434281.1	Q9NS37
	CREBZF	ENST00000850607.1		c.927G>C	p.Pro309Pro	synonymous	Exon 1 of 1	ENSP00000520895.1	Q9NS37

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.9
DANN	Benign	0.86
PhyloP100		-0.41

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-85374993;