10-31502731-C-T

Variant names:

• chr10-31502731-C-T
• rs220057
• NM_001174096.2:c.484+222C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001174096.2(ZEB1):​c.484+222C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,106 control chromosomes in the GnomAD database, including 52,386 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 0.81 (52386 hom., cov: 32)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB1	NM_001174096.2	c.484+222C>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+222C>T		intron_variant	Intron 4 of 8	5	NM_001174096.2	ENSP00000415961.2

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122450 AN: 151988 Hom.: 52367 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.805 AC: 122502 AN: 152106 Hom.: 52386 Cov.: 32 AF XY: 0.806 AC XY: 59964 AN XY: 74386

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.906

Gnomad4 ASJ AF: 0.935

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.928

Gnomad4 NFE AF: 0.947

Gnomad4 OTH AF: 0.841

Alfa AF: 0.862 Hom.: 7294

Bravo AF: 0.788

Asia WGS AF: 0.825 AC: 2870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.060
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs220057; hg19: chr10-31791659;