NM_001174096.2:c.59-4327G>A

Variant names:

• chr10-31456710-G-A
• rs161272
• NM_001174096.2:c.59-4327G>A

Variant summary

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

The NM_001174096.2(ZEB1):​c.59-4327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,940 control chromosomes in the GnomAD database, including 14,098 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 (14098 hom., cov: 32)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB1	NM_001174096.2	c.59-4327G>A		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.59-4327G>A		intron_variant	Intron 1 of 8	5	NM_001174096.2	ENSP00000415961.2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42788 AN: 151822 Hom.: 14040 Cov.: 32

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0721

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0574

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.282 AC: 42892 AN: 151940 Hom.: 14098 Cov.: 32 AF XY: 0.278 AC XY: 20608 AN XY: 74258

African (AFR) AF: 0.803 AC: 33231 AN: 41398

American (AMR) AF: 0.139 AC: 2124 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 516 AN: 3468

East Asian (EAS) AF: 0.201 AC: 1038 AN: 5164

South Asian (SAS) AF: 0.162 AC: 776 AN: 4804

European-Finnish (FIN) AF: 0.0721 AC: 763 AN: 10576

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.0573 AC: 3896 AN: 67974

Other (OTH) AF: 0.229 AC: 482 AN: 2108

Alfa AF: 0.216 Hom.: 1672

Bravo AF: 0.312

Asia WGS AF: 0.196 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.013
DANN	Benign	0.48
PhyloP100		-2.2
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: rs161272; hg19: chr10-31745639;