rs7221595

Positions:

• chr17-4104300-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015113.4(ZZEF1):​c.1573+333A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,078 control chromosomes in the GnomAD database, including 2,171 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 0.17 (2171 hom., cov: 31)
• Consequence: ZZEF1 NM_015113.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZZEF1	NM_015113.4	c.1573+333A>G		intron_variant		ENST00000381638.7	NP_055928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZZEF1	ENST00000381638.7	c.1573+333A>G		intron_variant		1	NM_015113.4	ENSP00000371051	P1
ZZEF1	ENST00000574474.1	n.1698+333A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25318 AN: 151960 Hom.: 2162 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.167 AC: 25366 AN: 152078 Hom.: 2171 Cov.: 31 AF XY: 0.165 AC XY: 12297 AN XY: 74352

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.168

Alfa AF: 0.169 Hom.: 377

Bravo AF: 0.166

Asia WGS AF: 0.165 AC: 574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.77

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: rs7221595; hg19: chr17-4007594;