rs7349

Variant names:

• chr10-31528977-C-T
• rs7349
• ENST00000437844.6:n.*5228C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000437844.6(ZEB1):​n.*5228C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,094 control chromosomes in the GnomAD database, including 14,102 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 (14102 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ZEB1 ENST00000437844.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 17 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=-0.49).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB1	NM_001174096.2	c.*1713C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000424869.6	NP_001167567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZEB1	ENST00000424869.6	c.*1713C>T		3_prime_UTR_variant	Exon 9 of 9	5	NM_001174096.2	ENSP00000415961.2

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42224 AN: 151976 Hom.: 14043 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0716

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0543

Gnomad OTH AF: 0.223

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.278 AC: 42330 AN: 152094 Hom.: 14102 Cov.: 32 AF XY: 0.273 AC XY: 20329 AN XY: 74362

African (AFR) AF: 0.804 AC: 33353 AN: 41484

American (AMR) AF: 0.130 AC: 1988 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0655 AC: 227 AN: 3464

East Asian (EAS) AF: 0.201 AC: 1038 AN: 5166

South Asian (SAS) AF: 0.157 AC: 756 AN: 4826

European-Finnish (FIN) AF: 0.0716 AC: 757 AN: 10570

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

European-Non Finnish (NFE) AF: 0.0542 AC: 3686 AN: 67976

Other (OTH) AF: 0.221 AC: 466 AN: 2110

Alfa AF: 0.134 Hom.: 12498

Bravo AF: 0.307

Asia WGS AF: 0.193 AC: 671 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		1.8
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: rs7349; hg19: chr10-31817905;