10-31366839-C-T

Variant names:

• chr10-31366839-C-T
• rs2839657
• NM_001174096.2:c.58+47547C>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+47547C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,994 control chromosomes in the GnomAD database, including 27,885 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 0.57 (27885 hom., cov: 31)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241
• 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: 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB1	NM_001174096.2	c.58+47547C>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+47547C>T		intron_variant	Intron 1 of 8	5	NM_001174096.2	ENSP00000415961.2

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86999 AN: 151872 Hom.: 27831 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.558

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.573 AC: 87108 AN: 151994 Hom.: 27885 Cov.: 31 AF XY: 0.568 AC XY: 42169 AN XY: 74260

African (AFR) AF: 0.880 AC: 36524 AN: 41500

American (AMR) AF: 0.414 AC: 6322 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1702 AN: 3460

East Asian (EAS) AF: 0.573 AC: 2956 AN: 5158

South Asian (SAS) AF: 0.491 AC: 2359 AN: 4802

European-Finnish (FIN) AF: 0.440 AC: 4638 AN: 10530

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30841 AN: 67962

Other (OTH) AF: 0.539 AC: 1137 AN: 2110

Alfa AF: 0.489 Hom.: 11675

Bravo AF: 0.588

Asia WGS AF: 0.519 AC: 1807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.7
DANN	Benign	0.60
PhyloP100		0.24
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: rs2839657; hg19: chr10-31655768;