10-31510794-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001174096.2(ZEB1):c.606T>C(p.Ser202=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,613,988 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (64 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (64 hom.)
• Consequence: ZEB1 NM_001174096.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.534

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 10-31510794-T-C is Benign according to our data. Variant chr10-31510794-T-C is described in ClinVar as [Benign]. Clinvar id is 788562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.534 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB1	NM_001174096.2	c.606T>C	p.Ser202=	synonymous_variant	5/9	ENST00000424869.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB1	ENST00000424869.6	c.606T>C	p.Ser202=	synonymous_variant	5/9	5	NM_001174096.2	A2

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2570 AN: 152220 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00436 AC: 1096 AN: 251148 Hom.: 30 AF XY: 0.00317 AC XY: 430 AN XY: 135716

Gnomad AFR exome AF: 0.0578

Gnomad AMR exome AF: 0.00341

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00170 AC: 2488 AN: 1461650 Hom.: 64 Cov.: 31 AF XY: 0.00143 AC XY: 1043 AN XY: 727132

Gnomad4 AFR exome AF: 0.0586

Gnomad4 AMR exome AF: 0.00394

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000719

Gnomad4 OTH exome AF: 0.00392

GnomAD4 genome AF: 0.0170 AC: 2587 AN: 152338 Hom.: 64 Cov.: 32 AF XY: 0.0157 AC XY: 1168 AN XY: 74508

Gnomad4 AFR AF: 0.0588

Gnomad4 AMR AF: 0.00660

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0113

Alfa AF: 0.00806 Hom.: 18

Bravo AF: 0.0193

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000296

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

Oct 08, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	8.1
Dann	Benign	0.70

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: rs79134358; hg19: chr10-31799722;