rs2839658

Positions:

• chr10-31367120-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+47828C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,976 control chromosomes in the GnomAD database, including 4,659 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 0.22 (4659 hom., cov: 31)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZEB1	NM_001174096.2	c.58+47828C>T		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+47828C>T		intron_variant		5	NM_001174096.2	ENSP00000415961.2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33773 AN: 151858 Hom.: 4655 Cov.: 31

Gnomad AFR AF: 0.0608

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.222 AC: 33780 AN: 151976 Hom.: 4659 Cov.: 31 AF XY: 0.226 AC XY: 16780 AN XY: 74240

Gnomad4 AFR AF: 0.0605

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.265

Alfa AF: 0.260 Hom.: 3348

Bravo AF: 0.203

Asia WGS AF: 0.395 AC: 1370 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.62

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: rs2839658; hg19: chr10-31656049;