ENST00000563190.1:n.222-6889C>T

Variant names:

• chr16-88287830-C-T
• rs6540223
• ENST00000563190.1:n.222-6889C>T

Variant summary

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

The ENST00000563190.1(LINC02182):​n.222-6889C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 152,068 control chromosomes in the GnomAD database, including 40,137 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 0.72 (40137 hom., cov: 32)
• Consequence: LINC02182 ENST00000563190.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• Publications: 18 publications found

Genes affected

LINC02182 (HGNC:53044): (long intergenic non-protein coding RNA 2182)

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000563190.1. You can select a different transcript below to see updated ACMG assignments.

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
	LINC02182	ENST00000563190.1	TSL:3	n.222-6889C>T		intron	N/A
	LINC02182	ENST00000718466.1		n.242-6889C>T		intron	N/A
	LINC02182	ENST00000767800.1		n.245+11255C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109552 AN: 151950 Hom.: 40078 Cov.: 32

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.721 AC: 109669 AN: 152068 Hom.: 40137 Cov.: 32 AF XY: 0.722 AC XY: 53692 AN XY: 74340

African (AFR) AF: 0.827 AC: 34303 AN: 41494

American (AMR) AF: 0.778 AC: 11867 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1937 AN: 3464

East Asian (EAS) AF: 0.939 AC: 4858 AN: 5174

South Asian (SAS) AF: 0.649 AC: 3125 AN: 4816

European-Finnish (FIN) AF: 0.671 AC: 7087 AN: 10566

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44292 AN: 67978

Other (OTH) AF: 0.713 AC: 1507 AN: 2114

Alfa AF: 0.697 Hom.: 25794

Bravo AF: 0.736

Asia WGS AF: 0.802 AC: 2780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.79
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs6540223; hg19: chr16-88321436;