rs220060

Positions:

• chr10-31514588-G-A
• chr10-31514588-G-C
• chr10-31514588-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001174096.2(ZEB1):​c.688-15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 1,608,802 control chromosomes in the GnomAD database, including 724,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64874 hom., cov: 32)
  • Exomes 𝑓: 0.95 (659401 hom.)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.521

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 10-31514588-G-A is Benign according to our data. Variant chr10-31514588-G-A is described in ClinVar as [Benign]. Clinvar id is 1601051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-31514588-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZEB1	NM_001174096.2	c.688-15G>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.688-15G>A		intron_variant		5	NM_001174096.2	ENSP00000415961.2

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140201 AN: 152058 Hom.: 64828 Cov.: 32

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.959

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.930

GnomAD3 exomes AF: 0.946 AC: 236204 AN: 249692 Hom.: 111883 AF XY: 0.946 AC XY: 127710 AN XY: 134966

Gnomad AFR exome AF: 0.834

Gnomad AMR exome AF: 0.974

Gnomad ASJ exome AF: 0.946

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.930

Gnomad FIN exome AF: 0.929

Gnomad NFE exome AF: 0.952

Gnomad OTH exome AF: 0.952

GnomAD4 exome AF: 0.951 AC: 1385516 AN: 1456626 Hom.: 659401 Cov.: 30 AF XY: 0.950 AC XY: 688769 AN XY: 724892

Gnomad4 AFR exome AF: 0.827

Gnomad4 AMR exome AF: 0.972

Gnomad4 ASJ exome AF: 0.947

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.928

Gnomad4 FIN exome AF: 0.934

Gnomad4 NFE exome AF: 0.956

Gnomad4 OTH exome AF: 0.944

GnomAD4 genome AF: 0.922 AC: 140306 AN: 152176 Hom.: 64874 Cov.: 32 AF XY: 0.921 AC XY: 68529 AN XY: 74400

Gnomad4 AFR AF: 0.838

Gnomad4 AMR AF: 0.959

Gnomad4 ASJ AF: 0.951

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.934

Gnomad4 FIN AF: 0.931

Gnomad4 NFE AF: 0.954

Gnomad4 OTH AF: 0.930

Alfa AF: 0.942 Hom.: 33291

Bravo AF: 0.921

Asia WGS AF: 0.966 AC: 3351 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.80

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: rs220060; hg19: chr10-31803516;