NM_001174096.2:c.259+13113C>A

Variant names:

• chr10-31474350-C-A
• rs220039
• NM_001174096.2:c.259+13113C>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.259+13113C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 150,972 control chromosomes in the GnomAD database, including 13,782 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 (13782 hom., cov: 29)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 2 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 = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB1	NM_001174096.2	c.259+13113C>A		intron_variant	Intron 2 of 8	ENST00000424869.6	NP_001167567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZEB1	ENST00000424869.6	c.259+13113C>A		intron_variant	Intron 2 of 8	5	NM_001174096.2	ENSP00000415961.2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41422 AN: 150856 Hom.: 13724 Cov.: 29

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0652

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0714

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.275 AC: 41526 AN: 150972 Hom.: 13782 Cov.: 29 AF XY: 0.270 AC XY: 19943 AN XY: 73822

African (AFR) AF: 0.802 AC: 32667 AN: 40724

American (AMR) AF: 0.129 AC: 1956 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0652 AC: 226 AN: 3466

East Asian (EAS) AF: 0.198 AC: 1016 AN: 5134

South Asian (SAS) AF: 0.154 AC: 736 AN: 4784

European-Finnish (FIN) AF: 0.0714 AC: 751 AN: 10522

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0538 AC: 3651 AN: 67840

Other (OTH) AF: 0.220 AC: 464 AN: 2106

Alfa AF: 0.186 Hom.: 1020

Bravo AF: 0.307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.038
DANN	Benign	0.54
PhyloP100		-2.1
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: rs220039; hg19: chr10-31763279;