chr16-88287830-C-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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF469	XM_047434810.1	c.-192+11255C>T		intron_variant	Intron 2 of 3		XP_047290766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC02182	ENST00000563190.1	n.222-6889C>T		intron_variant	Intron 2 of 3	3
LINC02182	ENST00000718466.1	n.242-6889C>T		intron_variant	Intron 2 of 3
LINC02182	ENST00000767800.1	n.245+11255C>T		intron_variant	Intron 2 of 2

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 v4.3

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;