rs220060

Variant names:

• chr10-31514588-G-A
• rs220060
• NM_001174096.2:c.688-15G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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: G2P, Labcorp Genetics (formerly Invitae)
• 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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1601051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB1	NM_001174096.2	MANE Select	c.688-15G>A		intron	N/A	NP_001167567.1
	ZEB1	NM_030751.6		c.685-15G>A		intron	N/A	NP_110378.3
	ZEB1	NM_001323676.2		c.646-15G>A		intron	N/A	NP_001310605.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB1	ENST00000424869.6	TSL:5 MANE Select	c.688-15G>A		intron	N/A	ENSP00000415961.2
	ZEB1	ENST00000320985.14	TSL:1	c.685-15G>A		intron	N/A	ENSP00000319248.9
	ZEB1	ENST00000558440.5	TSL:1	c.463-15G>A		intron	N/A	ENSP00000453970.1

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

GnomAD2 exomes AF: 0.946 AC: 236204 AN: 249692 AF XY: 0.946

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 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

African (AFR) AF: 0.827 AC: 27560 AN: 33330

American (AMR) AF: 0.972 AC: 43359 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 24654 AN: 26044

East Asian (EAS) AF: 1.00 AC: 39526 AN: 39530

South Asian (SAS) AF: 0.928 AC: 79842 AN: 86044

European-Finnish (FIN) AF: 0.934 AC: 49668 AN: 53158

Middle Eastern (MID) AF: 0.934 AC: 5338 AN: 5716

European-Non Finnish (NFE) AF: 0.956 AC: 1058771 AN: 1108038

Other (OTH) AF: 0.944 AC: 56798 AN: 60156

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

African (AFR) AF: 0.838 AC: 34827 AN: 41536

American (AMR) AF: 0.959 AC: 14656 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.951 AC: 3300 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5179 AN: 5180

South Asian (SAS) AF: 0.934 AC: 4508 AN: 4824

European-Finnish (FIN) AF: 0.931 AC: 9872 AN: 10598

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.954 AC: 64823 AN: 67966

Other (OTH) AF: 0.930 AC: 1963 AN: 2110

Alfa AF: 0.943 Hom.: 36792

Bravo AF: 0.921

Asia WGS AF: 0.966 AC: 3351 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs220060; hg19: chr10-31803516;