10-31506284-C-T

Variant names:

• chr10-31506284-C-T
• rs1618092
• NM_001174096.2:c.484+3775C>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+3775C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,808 control chromosomes in the GnomAD database, including 16,509 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 0.42 (16509 hom., cov: 32)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB1	NM_001174096.2	c.484+3775C>T		intron_variant	Intron 4 of 8	ENST00000424869.6	NP_001167567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZEB1	ENST00000424869.6	c.484+3775C>T		intron_variant	Intron 4 of 8	5	NM_001174096.2	ENSP00000415961.2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64285 AN: 151690 Hom.: 16505 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.423 AC: 64289 AN: 151808 Hom.: 16509 Cov.: 32 AF XY: 0.430 AC XY: 31903 AN XY: 74196

African (AFR) AF: 0.118 AC: 4877 AN: 41450

American (AMR) AF: 0.581 AC: 8861 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1757 AN: 3466

East Asian (EAS) AF: 0.508 AC: 2625 AN: 5164

South Asian (SAS) AF: 0.510 AC: 2459 AN: 4818

European-Finnish (FIN) AF: 0.554 AC: 5841 AN: 10542

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36343 AN: 67796

Other (OTH) AF: 0.457 AC: 964 AN: 2108

Alfa AF: 0.506 Hom.: 25002

Bravo AF: 0.409

Asia WGS AF: 0.496 AC: 1724 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.9
DANN	Benign	0.55
PhyloP100		-0.52
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: rs1618092; hg19: chr10-31795212;