10-31469329-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001174096.2(ZEB1):c.259+8092C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 147,318 control chromosomes in the GnomAD database, including 61,615 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 0.91 (61615 hom., cov: 31)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

Genes affected

ZEB1 (HGNC:11642): (zinc finger E-box binding homeobox 1) This gene encodes a zinc finger transcription factor. The encoded protein likely plays a role in transcriptional repression of interleukin 2. Mutations in this gene have been associated with posterior polymorphous corneal dystrophy-3 and late-onset Fuchs endothelial corneal dystrophy. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB1	NM_001174096.2	c.259+8092C>G		intron_variant		ENST00000424869.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB1	ENST00000424869.6	c.259+8092C>G		intron_variant		5	NM_001174096.2	A2

Frequencies

GnomAD3 genomes AF: 0.914 AC: 134510 AN: 147204 Hom.: 61571 Cov.: 31

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.983

Gnomad AMR AF: 0.953

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.920

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

GnomAD4 genome AF: 0.914 AC: 134611 AN: 147318 Hom.: 61615 Cov.: 31 AF XY: 0.912 AC XY: 65605 AN XY: 71912

Gnomad4 AFR AF: 0.827

Gnomad4 AMR AF: 0.953

Gnomad4 ASJ AF: 0.946

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.920

Gnomad4 NFE AF: 0.947

Gnomad4 OTH AF: 0.921

Alfa AF: 0.921 Hom.: 1974

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.81
Dann	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs220048; hg19: chr10-31758258;