NM_001174096.2:c.192C>T

Variant names:

• chr10-31461170-C-T
• rs7918614
• NM_001174096.2:c.192C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001174096.2(ZEB1):​c.192C>T​(p.Asp64Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 1,613,300 control chromosomes in the GnomAD database, including 1,721 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (722 hom., cov: 32)
  • Exomes 𝑓: 0.015 (999 hom.)
• Consequence: ZEB1 NM_001174096.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.09
• Publications: 14 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: 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

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 10-31461170-C-T is Benign according to our data. Variant chr10-31461170-C-T is described in ClinVar as Benign. ClinVar VariationId is 1599567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB1	NM_001174096.2	MANE Select	c.192C>T	p.Asp64Asp	synonymous	Exon 2 of 9	NP_001167567.1	P37275-2
	ZEB1	NM_030751.6		c.192C>T	p.Asp64Asp	synonymous	Exon 2 of 9	NP_110378.3
	ZEB1	NM_001323676.2		c.150C>T	p.Asp50Asp	synonymous	Exon 2 of 9	NP_001310605.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB1	ENST00000424869.6	TSL:5 MANE Select	c.192C>T	p.Asp64Asp	synonymous	Exon 2 of 9	ENSP00000415961.2	P37275-2
	ZEB1	ENST00000320985.14	TSL:1	c.192C>T	p.Asp64Asp	synonymous	Exon 2 of 9	ENSP00000319248.9	P37275-1
	ZEB1	ENST00000558440.5	TSL:1	c.192C>T	p.Asp64Asp	synonymous	Exon 2 of 5	ENSP00000453970.1	H0YND9

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8851 AN: 151926 Hom.: 720 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0288

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.0713

Gnomad FIN AF: 0.00303

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00591

Gnomad OTH AF: 0.0498

GnomAD2 exomes AF: 0.0285 AC: 7140 AN: 250906 AF XY: 0.0274

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.0158

Gnomad ASJ exome AF: 0.0134

Gnomad EAS exome AF: 0.0239

Gnomad FIN exome AF: 0.00430

Gnomad NFE exome AF: 0.00618

Gnomad OTH exome AF: 0.0224

GnomAD4 exome AF: 0.0147 AC: 21449 AN: 1461256 Hom.: 999 Cov.: 31 AF XY: 0.0160 AC XY: 11605 AN XY: 726912

African (AFR) AF: 0.190 AC: 6342 AN: 33456

American (AMR) AF: 0.0179 AC: 796 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 344 AN: 26116

East Asian (EAS) AF: 0.0205 AC: 814 AN: 39642

South Asian (SAS) AF: 0.0694 AC: 5985 AN: 86214

European-Finnish (FIN) AF: 0.00401 AC: 214 AN: 53410

Middle Eastern (MID) AF: 0.0496 AC: 286 AN: 5766

European-Non Finnish (NFE) AF: 0.00450 AC: 5006 AN: 1111720

Other (OTH) AF: 0.0275 AC: 1662 AN: 60362

GnomAD4 genome AF: 0.0583 AC: 8861 AN: 152044 Hom.: 722 Cov.: 32 AF XY: 0.0571 AC XY: 4248 AN XY: 74334

African (AFR) AF: 0.177 AC: 7358 AN: 41472

American (AMR) AF: 0.0288 AC: 439 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3472

East Asian (EAS) AF: 0.0235 AC: 122 AN: 5182

South Asian (SAS) AF: 0.0706 AC: 340 AN: 4818

European-Finnish (FIN) AF: 0.00303 AC: 32 AN: 10556

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00590 AC: 401 AN: 67970

Other (OTH) AF: 0.0493 AC: 104 AN: 2110

Alfa AF: 0.0299 Hom.: 219

Bravo AF: 0.0652

Asia WGS AF: 0.0570 AC: 199 AN: 3476

EpiCase AF: 0.00862

EpiControl AF: 0.00896

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	-0.44
CADD	Benign	7.8
DANN	Uncertain	0.99
PhyloP100		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs7918614; hg19: chr10-31750099;