rs7894637

Positions:

• chr10-31458887-T-C

Variant summary

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

The NM_001174096.2(ZEB1):​c.59-2150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,038 control chromosomes in the GnomAD database, including 10,373 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 0.25 (10373 hom., cov: 32)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZEB1	NM_001174096.2	c.59-2150T>C		intron_variant		ENST00000424869.6	NP_001167567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZEB1	ENST00000424869.6	c.59-2150T>C		intron_variant		5	NM_001174096.2	ENSP00000415961	A2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37651 AN: 151920 Hom.: 10320 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0725

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0570

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.248 AC: 37751 AN: 152038 Hom.: 10373 Cov.: 32 AF XY: 0.245 AC XY: 18201 AN XY: 74334

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0725

Gnomad4 NFE AF: 0.0570

Gnomad4 OTH AF: 0.202

Alfa AF: 0.177 Hom.: 1065

Bravo AF: 0.273

Asia WGS AF: 0.187 AC: 652 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.53
DANN	Benign	0.44

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: rs7894637; hg19: chr10-31747816;