10-31500787-C-T

Variant names:

• chr10-31500787-C-T
• rs220059
• NM_001174096.2:c.323-1561C>T

Variant summary

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

The NM_001174096.2(ZEB1):​c.323-1561C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 152,230 control chromosomes in the GnomAD database, including 64,906 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 0.92 (64906 hom., cov: 31)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 6 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: Labcorp Genetics (formerly Invitae), G2P
• 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 (EAS) allele frequency at 95% confidence interval = 0.977 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB1	NM_001174096.2	MANE Select	c.323-1561C>T		intron	N/A	NP_001167567.1	P37275-2
	ZEB1	NM_030751.6		c.320-1561C>T		intron	N/A	NP_110378.3
	ZEB1	NM_001323676.2		c.281-1561C>T		intron	N/A	NP_001310605.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB1	ENST00000424869.6	TSL:5 MANE Select	c.323-1561C>T		intron	N/A	ENSP00000415961.2	P37275-2
	ZEB1	ENST00000320985.14	TSL:1	c.320-1561C>T		intron	N/A	ENSP00000319248.9	P37275-1
	ZEB1	ENST00000558440.5	TSL:1	c.260-9886C>T		intron	N/A	ENSP00000453970.1	H0YND9

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140257 AN: 152112 Hom.: 64860 Cov.: 31

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.959

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.930

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

GnomAD4 genome AF: 0.922 AC: 140362 AN: 152230 Hom.: 64906 Cov.: 31 AF XY: 0.921 AC XY: 68557 AN XY: 74430

African (AFR) AF: 0.839 AC: 34808 AN: 41508

American (AMR) AF: 0.959 AC: 14667 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.951 AC: 3302 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5173 AN: 5174

South Asian (SAS) AF: 0.935 AC: 4514 AN: 4830

European-Finnish (FIN) AF: 0.931 AC: 9873 AN: 10604

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.954 AC: 64881 AN: 68026

Other (OTH) AF: 0.930 AC: 1967 AN: 2114

Alfa AF: 0.942 Hom.: 33286

Bravo AF: 0.921

Asia WGS AF: 0.966 AC: 3360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.17
DANN	Benign	0.74
PhyloP100		-1.9
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: rs220059; hg19: chr10-31789715;