rs161229

Variant names:

• chr10-31381633-A-G
• rs161229
• NM_001174096.2:c.58+62341A>G

Variant summary

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

The NM_001174096.2(ZEB1):​c.58+62341A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,112 control chromosomes in the GnomAD database, including 10,402 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 0.25 (10402 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 0 publications found

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]

ZEB1 Gene-Disease associations (from GenCC):

• posterior polymorphous corneal dystrophy 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Fuchs' endothelial dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• posterior polymorphous corneal dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• corneal dystrophy, Fuchs endothelial, 6

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB1	NM_001174096.2	c.58+62341A>G		intron_variant	Intron 1 of 8	ENST00000424869.6	NP_001167567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZEB1	ENST00000424869.6	c.58+62341A>G		intron_variant	Intron 1 of 8	5	NM_001174096.2	ENSP00000415961.2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37714 AN: 151994 Hom.: 10348 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.249 AC: 37814 AN: 152112 Hom.: 10402 Cov.: 31 AF XY: 0.245 AC XY: 18241 AN XY: 74374

African (AFR) AF: 0.686 AC: 28450 AN: 41452

American (AMR) AF: 0.123 AC: 1884 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 515 AN: 3464

East Asian (EAS) AF: 0.207 AC: 1070 AN: 5174

South Asian (SAS) AF: 0.162 AC: 779 AN: 4818

European-Finnish (FIN) AF: 0.0720 AC: 763 AN: 10598

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.0568 AC: 3862 AN: 68012

Other (OTH) AF: 0.202 AC: 427 AN: 2114

Alfa AF: 0.154 Hom.: 10588

Bravo AF: 0.273

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.68
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs161229; hg19: chr10-31670562;