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: 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF469	XM_047434810.1	c.-192+54302T>G		intron_variant	Intron 2 of 3		XP_047290766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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 v4.3

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;