Variant chr16-88427453-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001367624.2(ZNF469):c.-18C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0061 in 1,483,026 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0064 ( 45 hom. )

Consequence

ZNF469
NM_001367624.2 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.433

Variant links:

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 links:

LOC112268182 (HGNC:):

LOC112268182 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 16-88427453-C-A is Benign according to our data. Variant chr16-88427453-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 390584.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0038 (579/152246) while in subpopulation NFE AF= 0.00655 (445/67972). AF 95% confidence interval is 0.00604. There are 1 homozygotes in gnomad4. There are 289 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ZNF469	NM_001367624.2 linkuse as main transcript	c.-18C>A	5_prime_UTR_variant	3/3	ENST00000565624.3
LOC112268182	XR_007065178.1 linkuse as main transcript	n.251-1187G>T	intron_variant, non_coding_transcript_variant
ZNF469	XM_047434810.1 linkuse as main transcript	c.-18C>A	5_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF469	ENST00000565624.3 linkuse as main transcript	c.-18C>A		5_prime_UTR_variant	3/3		NM_001367624.2	A2
ZNF469	ENST00000437464.1 linkuse as main transcript			upstream_gene_variant		5		P4

Frequencies

GnomAD3 genomes

AF:

0.00379

AC:

576

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00574

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00655

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00340

AC:

322

AN:

94606

Hom.:

AF XY:

0.00360

AC XY:

183

AN XY:

50862

show subpopulations

Gnomad AFR exome

AF:

0.00102

Gnomad AMR exome

AF:

0.000871

Gnomad ASJ exome

AF:

0.00265

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000470

Gnomad FIN exome

AF:

0.00804

Gnomad NFE exome

AF:

0.00726

Gnomad OTH exome

AF:

0.00201

GnomAD4 exome

AF:

0.00636

AC:

8467

AN:

1330780

Hom.:

Cov.:

AF XY:

0.00619

AC XY:

4024

AN XY:

650554

show subpopulations

Gnomad4 AFR exome

AF:

0.00130

Gnomad4 AMR exome

AF:

0.000902

Gnomad4 ASJ exome

AF:

0.00166

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000867

Gnomad4 FIN exome

AF:

0.00652

Gnomad4 NFE exome

AF:

0.00750

Gnomad4 OTH exome

AF:

0.00368

GnomAD4 genome

AF:

0.00380

AC:

579

AN:

152246

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

289

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00574

Gnomad4 NFE

AF:

0.00655

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00238

Hom.:

Bravo

AF:

0.00323

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 16, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.5

DANN

Benign

0.87

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over