16-88313103-G-A

Variant names:

• chr16-88313103-G-A
• rs9927272
• XM_047434810.1:c.-192+36528G>A

Variant summary

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

The XM_047434810.1(ZNF469):​c.-192+36528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 151,624 control chromosomes in the GnomAD database, including 27,473 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 0.60 (27473 hom., cov: 32)
• Consequence: ZNF469 XM_047434810.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335
• Publications: 5 publications found

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]

ZNF469 Gene-Disease associations (from GenCC):

• brittle cornea syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp
• brittle cornea syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• aortic disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91162 AN: 151506 Hom.: 27440 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.602 AC: 91244 AN: 151624 Hom.: 27473 Cov.: 32 AF XY: 0.603 AC XY: 44654 AN XY: 74062

African (AFR) AF: 0.564 AC: 23357 AN: 41402

American (AMR) AF: 0.639 AC: 9752 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1884 AN: 3460

East Asian (EAS) AF: 0.755 AC: 3882 AN: 5142

South Asian (SAS) AF: 0.592 AC: 2845 AN: 4808

European-Finnish (FIN) AF: 0.596 AC: 6229 AN: 10452

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41323 AN: 67788

Other (OTH) AF: 0.618 AC: 1305 AN: 2112

Alfa AF: 0.607 Hom.: 45935

Bravo AF: 0.608

Asia WGS AF: 0.663 AC: 2300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.3
DANN	Benign	0.62
PhyloP100		0.34

Splicing

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

Other links and lift over

dbSNP: rs9927272; hg19: chr16-88346709;