Genetic Variant ENST00000636471.1:c.-488T>C (chr2-144520357-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The ENST00000636471.1(ZEB2):c.-488T>C variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0315 in 448,052 control chromosomes in the GnomAD database, including 314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.028 ( 102 hom., cov: 31)

Exomes 𝑓: 0.033 ( 212 hom. )

Consequence

ZEB2
ENST00000636471.1 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.38

Publications

2 publications found

Variant links:

Genes affected

ZEB2 (HGNC:14881): (zinc finger E-box binding homeobox 2) The protein encoded by this gene is a member of the Zfh1 family of 2-handed zinc finger/homeodomain proteins. It is located in the nucleus and functions as a DNA-binding transcriptional repressor that interacts with activated SMADs. Mutations in this gene are associated with Hirschsprung disease/Mowat-Wilson syndrome. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Jan 2010]

ZEB2 links:

ZEB2-AS1 (HGNC:37149): (ZEB2 antisense RNA 1) This gene produces a spliced long non-coding RNA which is a natural antisense transcript corresponding to the 5' UTR of zinc finger E-box binding homeobox 2 (ZEB2). It is thought that this transcript may be involved in the regulation of ZEB2 expression, and may play a role in the progression of bladder cancer. [provided by RefSeq, Aug 2015]

ZEB2-AS1 links:

ENSG00000273537 (HGNC:):

ENSG00000273537 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 2-144520357-A-G is Benign according to our data. Variant chr2-144520357-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 331305.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.028 (4263/152020) while in subpopulation NFE AF = 0.0397 (2700/67968). AF 95% confidence interval is 0.0385. There are 102 homozygotes in GnomAd4. There are 2082 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 4263 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636471.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZEB2-AS1	NR_040248.2		n.284+72A>G	intron	N/A
ZEB2	NM_014795.4	MANE Select	c.-488T>C	upstream_gene	N/A	NP_055610.1	O60315-1
ZEB2	NM_001171653.2		c.-488T>C	upstream_gene	N/A	NP_001165124.1	O60315-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZEB2	ENST00000636471.1	TSL:5	c.-488T>C	5_prime_UTR	Exon 1 of 10	ENSP00000490317.1	A0A1B0GV02
ZEB2	ENST00000886176.1		c.-75T>C	5_prime_UTR	Exon 1 of 10	ENSP00000556235.1
ZEB2	ENST00000886177.1		c.-275T>C	5_prime_UTR	Exon 1 of 10	ENSP00000556236.1

Frequencies

GnomAD3 genomes

AF:

0.0281

AC:

4265

AN:

151904

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00711

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0231

Gnomad ASJ

AF:

0.0945

Gnomad EAS

AF:

0.000774

Gnomad SAS

AF:

0.0191

Gnomad FIN

AF:

0.0369

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.0397

Gnomad OTH

AF:

0.0278

GnomAD2 exomes

AF:

0.0322

AC:

4263

AN:

132270

AF XY:

0.0325

show subpopulations

Gnomad AFR exome

AF:

0.00680

Gnomad AMR exome

AF:

0.0183

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0331

Gnomad NFE exome

AF:

0.0407

Gnomad OTH exome

AF:

0.0385

GnomAD4 exome

AF:

0.0333

AC:

9865

AN:

296032

Hom.:

212

Cov.:

AF XY:

0.0323

AC XY:

5449

AN XY:

168594

show subpopulations

African (AFR)

AF:

0.00799

AC:

AN:

8014

American (AMR)

AF:

0.0184

AC:

485

AN:

26296

Ashkenazi Jewish (ASJ)

AF:

0.0969

AC:

1026

AN:

10586

East Asian (EAS)

AF:

0.00

AC:

AN:

9136

South Asian (SAS)

AF:

0.0204

AC:

1204

AN:

59002

European-Finnish (FIN)

AF:

0.0306

AC:

387

AN:

12650

Middle Eastern (MID)

AF:

0.0271

AC:

AN:

1108

European-Non Finnish (NFE)

AF:

0.0397

AC:

6171

AN:

155554

Other (OTH)

AF:

0.0364

AC:

498

AN:

13686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

528

1055

1583

2110

2638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.0280

AC:

4263

AN:

152020

Hom.:

102

Cov.:

AF XY:

0.0280

AC XY:

2082

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.00709

AC:

294

AN:

41454

American (AMR)

AF:

0.0231

AC:

353

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0945

AC:

328

AN:

3470

East Asian (EAS)

AF:

0.000776

AC:

AN:

5154

South Asian (SAS)

AF:

0.0193

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0369

AC:

390

AN:

10576

Middle Eastern (MID)

AF:

0.0377

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0397

AC:

2700

AN:

67968

Other (OTH)

AF:

0.0266

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

195

390

586

781

976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0437

Hom.:

Bravo

AF:

0.0265

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely 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

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

4.4

PromoterAI

-0.070

Neutral

(source)

Mutation Taster

=295/5

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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