10-31461170-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001174096.2(ZEB1):c.192C>T(p.Asp64=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 1,613,300 control chromosomes in the GnomAD database, including 1,721 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.058 (722 hom., cov: 32)
  • Exomes 𝑓: 0.015 (999 hom.)
• Consequence: ZEB1 NM_001174096.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.09

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 10-31461170-C-T is Benign according to our data. Variant chr10-31461170-C-T is described in ClinVar as [Benign]. Clinvar id is 1599567.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB1	NM_001174096.2	c.192C>T	p.Asp64=	synonymous_variant	2/9	ENST00000424869.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB1	ENST00000424869.6	c.192C>T	p.Asp64=	synonymous_variant	2/9	5	NM_001174096.2	A2

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8851 AN: 151926 Hom.: 720 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0288

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.0713

Gnomad FIN AF: 0.00303

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00591

Gnomad OTH AF: 0.0498

GnomAD3 exomes AF: 0.0285 AC: 7140 AN: 250906 Hom.: 402 AF XY: 0.0274 AC XY: 3711 AN XY: 135586

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.0158

Gnomad ASJ exome AF: 0.0134

Gnomad EAS exome AF: 0.0239

Gnomad SAS exome AF: 0.0700

Gnomad FIN exome AF: 0.00430

Gnomad NFE exome AF: 0.00618

Gnomad OTH exome AF: 0.0224

GnomAD4 exome AF: 0.0147 AC: 21449 AN: 1461256 Hom.: 999 Cov.: 31 AF XY: 0.0160 AC XY: 11605 AN XY: 726912

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0179

Gnomad4 ASJ exome AF: 0.0132

Gnomad4 EAS exome AF: 0.0205

Gnomad4 SAS exome AF: 0.0694

Gnomad4 FIN exome AF: 0.00401

Gnomad4 NFE exome AF: 0.00450

Gnomad4 OTH exome AF: 0.0275

GnomAD4 genome AF: 0.0583 AC: 8861 AN: 152044 Hom.: 722 Cov.: 32 AF XY: 0.0571 AC XY: 4248 AN XY: 74334

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.0288

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.0235

Gnomad4 SAS AF: 0.0706

Gnomad4 FIN AF: 0.00303

Gnomad4 NFE AF: 0.00590

Gnomad4 OTH AF: 0.0493

Alfa AF: 0.0279 Hom.: 185

Bravo AF: 0.0652

Asia WGS AF: 0.0570 AC: 199 AN: 3476

EpiCase AF: 0.00862

EpiControl AF: 0.00896

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	7.8
Dann	Uncertain	0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs7918614; hg19: chr10-31750099;