10-31461077-AGAT-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BS1 BS2

The NM_001174096.2(ZEB1):c.105_107del(p.Asp35del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,613,390 control chromosomes in the GnomAD database, including 25 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (13 hom.)
• Consequence: ZEB1 NM_001174096.2 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.12

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 -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001174096.2. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 10-31461077-AGAT-A is Benign according to our data. Variant chr10-31461077-AGAT-A is described in ClinVar as [Benign]. Clinvar id is 785316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00698 (1063/152264) while in subpopulation AFR AF= 0.0235 (977/41572). AF 95% confidence interval is 0.0223. There are 12 homozygotes in gnomad4. There are 507 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1059 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB1	NM_001174096.2	c.105_107del	p.Asp35del	inframe_deletion	2/9	ENST00000424869.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB1	ENST00000424869.6	c.105_107del	p.Asp35del	inframe_deletion	2/9	5	NM_001174096.2	A2

Frequencies

GnomAD3 genomes AF: 0.00696 AC: 1059 AN: 152146 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00205 AC: 514 AN: 250904 Hom.: 6 AF XY: 0.00159 AC XY: 215 AN XY: 135616

Gnomad AFR exome AF: 0.0244

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000388

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.000905 AC: 1323 AN: 1461126 Hom.: 13 AF XY: 0.000805 AC XY: 585 AN XY: 726864

Gnomad4 AFR exome AF: 0.0245

Gnomad4 AMR exome AF: 0.00202

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000249

Gnomad4 OTH exome AF: 0.00172

GnomAD4 genome AF: 0.00698 AC: 1063 AN: 152264 Hom.: 12 Cov.: 32 AF XY: 0.00681 AC XY: 507 AN XY: 74456

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00378 Hom.: 2

Bravo AF: 0.00779

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000652

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 18, 2024

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Computational scores

Source: dbNSFP v4.3

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: rs141941188; hg19: chr10-31750006;