rs161254

Positions:

• chr10-31415643-C-T

Variant summary

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

The NM_001174096.2(ZEB1):​c.59-45394C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,004 control chromosomes in the GnomAD database, including 13,630 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 0.28 (13630 hom., cov: 32)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB1	NM_001174096.2	c.59-45394C>T		intron_variant		ENST00000424869.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB1	ENST00000424869.6	c.59-45394C>T		intron_variant		5	NM_001174096.2	A2

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42186 AN: 151886 Hom.: 13582 Cov.: 32

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0725

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.278 AC: 42275 AN: 152004 Hom.: 13630 Cov.: 32 AF XY: 0.273 AC XY: 20320 AN XY: 74334

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0725

Gnomad4 NFE AF: 0.0568

Gnomad4 OTH AF: 0.224

Alfa AF: 0.189 Hom.: 1020

Bravo AF: 0.307

Asia WGS AF: 0.188 AC: 649 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.82

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: rs161254; hg19: chr10-31704572;