rs7198446

Variant names:

• chr16-88345763-A-C
• rs7198446
• ENST00000744075.1:n.127T>G

Your query was ambiguous. Multiple possible variants found:

• chr16-88345763-A-C
• chr16-88345763-A-T

Variant summary

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

The ENST00000744075.1(ENSG00000296988):​n.127T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,974 control chromosomes in the GnomAD database, including 18,676 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 0.49 (18676 hom., cov: 32)
• Consequence: ENSG00000296988 ENST00000744075.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 4 publications found

Genes affected

ENSG00000296988 (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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF469	XM_047434810.1	c.-192+69188A>C		intron_variant	Intron 2 of 3		XP_047290766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000296988	ENST00000744075.1	n.127T>G		non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74341 AN: 151856 Hom.: 18641 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.490 AC: 74412 AN: 151974 Hom.: 18676 Cov.: 32 AF XY: 0.489 AC XY: 36331 AN XY: 74268

African (AFR) AF: 0.609 AC: 25249 AN: 41438

American (AMR) AF: 0.393 AC: 5994 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1737 AN: 3464

East Asian (EAS) AF: 0.332 AC: 1711 AN: 5158

South Asian (SAS) AF: 0.505 AC: 2421 AN: 4796

European-Finnish (FIN) AF: 0.466 AC: 4930 AN: 10580

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.454 AC: 30829 AN: 67950

Other (OTH) AF: 0.446 AC: 942 AN: 2114

Alfa AF: 0.456 Hom.: 26101

Bravo AF: 0.484

Asia WGS AF: 0.389 AC: 1358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.5
DANN	Benign	0.39
PhyloP100		-0.12

Splicing

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

Other links and lift over

dbSNP: rs7198446; hg19: chr16-88379369;