16-88427453-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001367624.2(ZNF469):c.-18C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0061 in 1,483,026 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0064 (45 hom.)
• Consequence: ZNF469 NM_001367624.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.433

Genes affected

ZNF469 (HGNC:23216): (zinc finger protein 469) This gene encodes a zinc-finger protein. Low-percent homology to certain collagens suggests that it may function as a transcription factor or extra-nuclear regulator factor for the synthesis or organization of collagen fibers. Mutations in this gene cause brittle cornea syndrome. [provided by RefSeq, Jul 2008]

LOC112268182 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 16-88427453-C-A is Benign according to our data. Variant chr16-88427453-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 390584.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0038 (579/152246) while in subpopulation NFE AF= 0.00655 (445/67972). AF 95% confidence interval is 0.00604. There are 1 homozygotes in gnomad4. There are 289 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF469	NM_001367624.2	c.-18C>A		5_prime_UTR_variant	3/3	ENST00000565624.3
LOC112268182	XR_007065178.1	n.251-1187G>T		intron_variant, non_coding_transcript_variant
ZNF469	XM_047434810.1	c.-18C>A		5_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF469	ENST00000565624.3	c.-18C>A		5_prime_UTR_variant	3/3		NM_001367624.2	A2
ZNF469	ENST00000437464.1			upstream_gene_variant		5		P4

Frequencies

GnomAD3 genomes AF: 0.00379 AC: 576 AN: 152128 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00574

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00655

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00340 AC: 322 AN: 94606 Hom.: 1 AF XY: 0.00360 AC XY: 183 AN XY: 50862

Gnomad AFR exome AF: 0.00102

Gnomad AMR exome AF: 0.000871

Gnomad ASJ exome AF: 0.00265

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000470

Gnomad FIN exome AF: 0.00804

Gnomad NFE exome AF: 0.00726

Gnomad OTH exome AF: 0.00201

GnomAD4 exome AF: 0.00636 AC: 8467 AN: 1330780 Hom.: 45 Cov.: 32 AF XY: 0.00619 AC XY: 4024 AN XY: 650554

Gnomad4 AFR exome AF: 0.00130

Gnomad4 AMR exome AF: 0.000902

Gnomad4 ASJ exome AF: 0.00166

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000867

Gnomad4 FIN exome AF: 0.00652

Gnomad4 NFE exome AF: 0.00750

Gnomad4 OTH exome AF: 0.00368

GnomAD4 genome AF: 0.00380 AC: 579 AN: 152246 Hom.: 1 Cov.: 34 AF XY: 0.00388 AC XY: 289 AN XY: 74432

Gnomad4 AFR AF: 0.000962

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00574

Gnomad4 NFE AF: 0.00655

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00238 Hom.: 0

Bravo AF: 0.00323

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 16, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	6.5
Dann	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs568661500; hg19: chr16-88493861;