rs17684886

Variant names:

• chr16-75052977-A-T
• rs17684886
• NM_032268.5:c.425-40595A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032268.5(ZNRF1):​c.425-40595A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,220 control chromosomes in the GnomAD database, including 1,993 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 0.12 (1993 hom., cov: 32)
• Consequence: ZNRF1 NM_032268.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.553
• Publications: 7 publications found

Genes affected

ZNRF1 (HGNC:18452): (zinc and ring finger 1) This gene encodes an E3 ubiquitin-protein ligase that plays a role in neural-cell differentiation. Overexpression of this gene causes neurite-like elongation. The encoded protein contains both a zinc finger and a RING finger motif and is localized in the endosome/lysosome compartment, indicating that it may be involved in ubiquitin-mediated protein modification, and in synaptic vessicle membranes in neurons. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNRF1	NM_032268.5	c.425-40595A>T		intron_variant	Intron 1 of 4	ENST00000335325.9	NP_115644.1
ZNRF1	XM_017023793.2	c.425-40595A>T		intron_variant	Intron 1 of 4		XP_016879282.1
ZNRF1	XM_011523392.2	c.425-31452A>T		intron_variant	Intron 1 of 1		XP_011521694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNRF1	ENST00000335325.9	c.425-40595A>T		intron_variant	Intron 1 of 4	1	NM_032268.5	ENSP00000335091.4

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18929 AN: 152102 Hom.: 1992 Cov.: 32

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.124 AC: 18925 AN: 152220 Hom.: 1993 Cov.: 32 AF XY: 0.130 AC XY: 9682 AN XY: 74416

African (AFR) AF: 0.0377 AC: 1567 AN: 41574

American (AMR) AF: 0.158 AC: 2417 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3466

East Asian (EAS) AF: 0.539 AC: 2778 AN: 5154

South Asian (SAS) AF: 0.333 AC: 1602 AN: 4818

European-Finnish (FIN) AF: 0.122 AC: 1293 AN: 10602

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8442 AN: 68000

Other (OTH) AF: 0.117 AC: 247 AN: 2116

Alfa AF: 0.117 Hom.: 183

Bravo AF: 0.123

Asia WGS AF: 0.387 AC: 1342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.22
DANN	Benign	0.64
PhyloP100		-0.55
Mutation Taster		=100/0	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: rs17684886; hg19: chr16-75086875;