rs7500421

Variant names:

• chr16-88330877-T-G
• rs7500421
• XM_047434810.1:c.-192+54302T>G

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+54302T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,092 control chromosomes in the GnomAD database, including 3,717 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 0.22 (3717 hom., cov: 33)
• Consequence: ZNF469 XM_047434810.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 3 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: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33069 AN: 151974 Hom.: 3696 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.218 AC: 33125 AN: 152092 Hom.: 3717 Cov.: 33 AF XY: 0.217 AC XY: 16163 AN XY: 74354

African (AFR) AF: 0.227 AC: 9421 AN: 41474

American (AMR) AF: 0.143 AC: 2183 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3466

East Asian (EAS) AF: 0.126 AC: 651 AN: 5180

South Asian (SAS) AF: 0.181 AC: 872 AN: 4814

European-Finnish (FIN) AF: 0.259 AC: 2741 AN: 10578

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15317 AN: 67978

Other (OTH) AF: 0.201 AC: 424 AN: 2112

Alfa AF: 0.222 Hom.: 11538

Bravo AF: 0.210

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.25
DANN	Benign	0.30
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs7500421; hg19: chr16-88364483;