16-88304501-T-C

Variant names:

• chr16-88304501-T-C
• rs9925231
• ENST00000768617.1:n.128+12A>G

Variant summary

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

The ENST00000768617.1(ENSG00000300066):​n.128+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 151,856 control chromosomes in the GnomAD database, including 31,196 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 0.64 (31196 hom., cov: 30)
• Consequence: ENSG00000300066 ENST00000768617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.60
• Publications: 9 publications found

Genes affected

ENSG00000300066 (HGNC:):

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF469	XM_047434810.1	c.-192+27926T>C		intron_variant	Intron 2 of 3		XP_047290766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000300066	ENST00000768617.1	n.128+12A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97157 AN: 151738 Hom.: 31164 Cov.: 30

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.640 AC: 97237 AN: 151856 Hom.: 31196 Cov.: 30 AF XY: 0.639 AC XY: 47381 AN XY: 74204

African (AFR) AF: 0.633 AC: 26194 AN: 41382

American (AMR) AF: 0.682 AC: 10416 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2053 AN: 3470

East Asian (EAS) AF: 0.777 AC: 3994 AN: 5138

South Asian (SAS) AF: 0.637 AC: 3054 AN: 4796

European-Finnish (FIN) AF: 0.582 AC: 6150 AN: 10574

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.638 AC: 43308 AN: 67904

Other (OTH) AF: 0.657 AC: 1387 AN: 2110

Alfa AF: 0.623 Hom.: 12680

Bravo AF: 0.649

Asia WGS AF: 0.678 AC: 2356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.67
DANN	Benign	0.45
PhyloP100		-3.6

Splicing

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

Other links and lift over

dbSNP: rs9925231; hg19: chr16-88338107;