rs9299657

Positions:

• chr10-31345784-G-A

Variant summary

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

The NM_001174096.2(ZEB1):​c.58+26492G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,084 control chromosomes in the GnomAD database, including 3,274 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 0.19 (3274 hom., cov: 32)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB1	NM_001174096.2	c.58+26492G>A		intron_variant		ENST00000424869.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB1	ENST00000424869.6	c.58+26492G>A		intron_variant		5	NM_001174096.2	A2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28222 AN: 151966 Hom.: 3270 Cov.: 32

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.186 AC: 28226 AN: 152084 Hom.: 3274 Cov.: 32 AF XY: 0.187 AC XY: 13936 AN XY: 74362

Gnomad4 AFR AF: 0.0525

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.213

Alfa AF: 0.205 Hom.: 614

Bravo AF: 0.172

Asia WGS AF: 0.224 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.30

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: rs9299657; hg19: chr10-31634713;