NM_001174096.2:c.484+222C>T

Variant names:

• chr10-31502731-C-T
• rs220057
• NM_001174096.2:c.484+222C>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.484+222C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,106 control chromosomes in the GnomAD database, including 52,386 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 0.81 (52386 hom., cov: 32)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.941 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.484+222C>T		intron	N/A	NP_001167567.1
	ZEB1	NM_030751.6		c.481+222C>T		intron	N/A	NP_110378.3
	ZEB1	NM_001323676.2		c.442+222C>T		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.484+222C>T		intron	N/A	ENSP00000415961.2
	ZEB1	ENST00000320985.14	TSL:1	c.481+222C>T		intron	N/A	ENSP00000319248.9
	ZEB1	ENST00000558440.5	TSL:1	c.260-7942C>T		intron	N/A	ENSP00000453970.1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122450 AN: 151988 Hom.: 52367 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.805 AC: 122502 AN: 152106 Hom.: 52386 Cov.: 32 AF XY: 0.806 AC XY: 59964 AN XY: 74386

African (AFR) AF: 0.483 AC: 20025 AN: 41418

American (AMR) AF: 0.906 AC: 13849 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 3245 AN: 3472

East Asian (EAS) AF: 0.799 AC: 4146 AN: 5188

South Asian (SAS) AF: 0.844 AC: 4072 AN: 4822

European-Finnish (FIN) AF: 0.928 AC: 9844 AN: 10608

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64392 AN: 68004

Other (OTH) AF: 0.841 AC: 1775 AN: 2110

Alfa AF: 0.862 Hom.: 7294

Bravo AF: 0.788

Asia WGS AF: 0.825 AC: 2870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.060
DANN	Benign	0.36
PhyloP100		-1.2
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: rs220057; hg19: chr10-31791659;