17-4066839-A-ATCCTATTCTACTCTGAAT

Variant names:

• chr17-4066839-A-ATCCTATTCTACTCTGAAT
• rs2307581
• NM_015113.4:c.4156-300_4156-299insATTCAGAGTAGAATAGGA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_015113.4(ZZEF1):​c.4156-300_4156-299insATTCAGAGTAGAATAGGA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (20843 hom., cov: 0)
• Consequence: ZZEF1 NM_015113.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 4 publications found

Genes affected

ZZEF1 (HGNC:29027): (zinc finger ZZ-type and EF-hand domain containing 1) Predicted to enable ubiquitin-like protein ligase activity. Predicted to act upstream of or within several processes, including glutamatergic synaptic transmission; regulation of peptidyl-tyrosine phosphorylation; and visual learning. Predicted to be located in cell surface; postsynapse; and presynaptic active zone. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZZEF1	NM_015113.4	c.4156-300_4156-299insATTCAGAGTAGAATAGGA		intron_variant	Intron 27 of 54	ENST00000381638.7	NP_055928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZZEF1	ENST00000381638.7	c.4156-300_4156-299insATTCAGAGTAGAATAGGA		intron_variant	Intron 27 of 54	1	NM_015113.4	ENSP00000371051.2
ZZEF1	ENST00000570365.1	n.415-300_415-299insATTCAGAGTAGAATAGGA		intron_variant	Intron 3 of 4	4
ZZEF1	ENST00000572426.5	n.314-300_314-299insATTCAGAGTAGAATAGGA		intron_variant	Intron 2 of 14	2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74920 AN: 151638 Hom.: 20786 Cov.: 0

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.462

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.494 AC: 75038 AN: 151756 Hom.: 20843 Cov.: 0 AF XY: 0.488 AC XY: 36193 AN XY: 74162

African (AFR) AF: 0.772 AC: 31895 AN: 41336

American (AMR) AF: 0.446 AC: 6793 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1275 AN: 3472

East Asian (EAS) AF: 0.264 AC: 1363 AN: 5166

South Asian (SAS) AF: 0.366 AC: 1758 AN: 4808

European-Finnish (FIN) AF: 0.379 AC: 3993 AN: 10536

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26421 AN: 67906

Other (OTH) AF: 0.461 AC: 969 AN: 2102

Alfa AF: 0.256 Hom.: 496

Asia WGS AF: 0.349 AC: 1215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2307581; hg19: chr17-3970133;