NM_001174096.2:c.59-2150T>C

Variant names:

• chr10-31458887-T-C
• rs7894637
• NM_001174096.2:c.59-2150T>C

Variant summary

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

The NM_001174096.2(ZEB1):​c.59-2150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,038 control chromosomes in the GnomAD database, including 10,373 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 (10373 hom., cov: 32)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174096.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB1	NM_001174096.2	MANE Select	c.59-2150T>C		intron	N/A	NP_001167567.1
	ZEB1	NM_030751.6		c.59-2150T>C		intron	N/A	NP_110378.3
	ZEB1	NM_001323676.2		c.17-2150T>C		intron	N/A	NP_001310605.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB1	ENST00000424869.6	TSL:5 MANE Select	c.59-2150T>C		intron	N/A	ENSP00000415961.2
	ZEB1	ENST00000320985.14	TSL:1	c.59-2150T>C		intron	N/A	ENSP00000319248.9
	ZEB1	ENST00000558440.5	TSL:1	c.59-2150T>C		intron	N/A	ENSP00000453970.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37651 AN: 151920 Hom.: 10320 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0725

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0570

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.248 AC: 37751 AN: 152038 Hom.: 10373 Cov.: 32 AF XY: 0.245 AC XY: 18201 AN XY: 74334

African (AFR) AF: 0.686 AC: 28422 AN: 41434

American (AMR) AF: 0.123 AC: 1876 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 515 AN: 3468

East Asian (EAS) AF: 0.200 AC: 1032 AN: 5162

South Asian (SAS) AF: 0.161 AC: 776 AN: 4826

European-Finnish (FIN) AF: 0.0725 AC: 769 AN: 10602

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0570 AC: 3872 AN: 67974

Other (OTH) AF: 0.202 AC: 426 AN: 2106

Alfa AF: 0.193 Hom.: 1250

Bravo AF: 0.273

Asia WGS AF: 0.187 AC: 652 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.53
DANN	Benign	0.44
PhyloP100		-1.8
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: rs7894637; hg19: chr10-31747816;