rs2839658

Variant names:

• chr10-31367120-C-T
• rs2839658
• NM_001174096.2:c.58+47828C>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.58+47828C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,976 control chromosomes in the GnomAD database, including 4,659 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 0.22 (4659 hom., cov: 31)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB1	NM_001174096.2	c.58+47828C>T		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.58+47828C>T		intron_variant	Intron 1 of 8	5	NM_001174096.2	ENSP00000415961.2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33773 AN: 151858 Hom.: 4655 Cov.: 31

Gnomad AFR AF: 0.0608

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.222 AC: 33780 AN: 151976 Hom.: 4659 Cov.: 31 AF XY: 0.226 AC XY: 16780 AN XY: 74240

African (AFR) AF: 0.0605 AC: 2512 AN: 41492

American (AMR) AF: 0.225 AC: 3440 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1031 AN: 3470

East Asian (EAS) AF: 0.347 AC: 1789 AN: 5158

South Asian (SAS) AF: 0.393 AC: 1889 AN: 4812

European-Finnish (FIN) AF: 0.305 AC: 3201 AN: 10506

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.279 AC: 18981 AN: 67948

Other (OTH) AF: 0.265 AC: 559 AN: 2110

Alfa AF: 0.260 Hom.: 4383

Bravo AF: 0.203

Asia WGS AF: 0.395 AC: 1370 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.62
PhyloP100		-0.12
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: rs2839658; hg19: chr10-31656049;