dbSNP rs141941188: ZEB1:p.Asp35del (chr10-31461077-AGAT-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PM4_SupportingBP6_ModerateBS1BS2

The NM_001174096.2(ZEB1):c.105_107delTGA(p.Asp35del) variant causes a disruptive 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 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.12

Publications

2 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

posterior polymorphous corneal dystrophy 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Fuchs' endothelial dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
posterior polymorphous corneal dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
corneal dystrophy, Fuchs endothelial, 6
Inheritance: AD Classification: LIMITED Submitted by: G2P

ZEB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1063 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174096.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZEB1	NM_001174096.2	MANE Select	c.105_107delTGA	p.Asp35del	disruptive_inframe_deletion	Exon 2 of 9	NP_001167567.1	P37275-2
ZEB1	NM_030751.6		c.105_107delTGA	p.Asp35del	disruptive_inframe_deletion	Exon 2 of 9	NP_110378.3
ZEB1	NM_001323676.2		c.63_65delTGA	p.Asp21del	disruptive_inframe_deletion	Exon 2 of 9	NP_001310605.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZEB1	ENST00000424869.6	TSL:5 MANE Select	c.105_107delTGA	p.Asp35del	disruptive_inframe_deletion	Exon 2 of 9	ENSP00000415961.2	P37275-2
ZEB1	ENST00000320985.14	TSL:1	c.105_107delTGA	p.Asp35del	disruptive_inframe_deletion	Exon 2 of 9	ENSP00000319248.9	P37275-1
ZEB1	ENST00000558440.5	TSL:1	c.105_107delTGA	p.Asp35del	disruptive_inframe_deletion	Exon 2 of 5	ENSP00000453970.1	H0YND9

Frequencies

GnomAD3 genomes

AF:

0.00696

AC:

1059

AN:

152146

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00205

AC:

514

AN:

250904

AF XY:

0.00159

show subpopulations

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 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.:

AF XY:

0.000805

AC XY:

585

AN XY:

726864

show subpopulations

African (AFR)

AF:

0.0245

AC:

819

AN:

33454

American (AMR)

AF:

0.00202

AC:

AN:

44574

Ashkenazi Jewish (ASJ)

AF:

0.0000766

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.000104

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00364

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000249

AC:

277

AN:

1111566

Other (OTH)

AF:

0.00172

AC:

104

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

125

187

250

312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00698

AC:

1063

AN:

152264

Hom.:

Cov.:

AF XY:

0.00681

AC XY:

507

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0235

AC:

977

AN:

41572

American (AMR)

AF:

0.00327

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68010

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

147

196

245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00378

Hom.:

Bravo

AF:

0.00779

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000652

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

8.1

Mutation Taster

=49/51

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over