16-88304501-T-C

Variant names:

• chr16-88304501-T-C
• rs9925231
• XM_047434810.1:c.-192+27926T>C

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

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, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• brittle cornea syndrome

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

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000300066 (HGNC:):

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000768617.1. You can select a different transcript below to see updated ACMG assignments.

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
	ENSG00000300066	ENST00000768617.1		n.128+12A>G		intron	N/A

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs9925231;

hg19: chr16-88338107;