rs431073

Positions:

• chr10-31388277-C-A
• chr10-31388277-C-G
• chr10-31388277-C-T

Variant summary

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

The NM_001174096.2(ZEB1):​c.58+68985C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 152,062 control chromosomes in the GnomAD database, including 53,073 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 0.83 (53073 hom., cov: 32)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZEB1	NM_001174096.2	c.58+68985C>A		intron_variant		ENST00000424869.6	NP_001167567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZEB1	ENST00000424869.6	c.58+68985C>A		intron_variant		5	NM_001174096.2	ENSP00000415961.2

Frequencies

GnomAD3 genomes AF: 0.829 AC: 125995 AN: 151944 Hom.: 53014 Cov.: 32

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.829 AC: 126114 AN: 152062 Hom.: 53073 Cov.: 32 AF XY: 0.827 AC XY: 61431 AN XY: 74314

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.926

Gnomad4 SAS AF: 0.916

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.839

Alfa AF: 0.791 Hom.: 31946

Bravo AF: 0.825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.11
DANN	Benign	0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs431073; hg19: chr10-31677206;