rs220049

Variant names:

• chr10-31468028-T-A
• rs220049
• NM_001174096.2:c.259+6791T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-31468028-T-A
• chr10-31468028-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001174096.2(ZEB1):​c.259+6791T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 151,822 control chromosomes in the GnomAD database, including 10,312 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (10312 hom., cov: 31)
• Consequence: ZEB1 NM_001174096.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 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.259+6791T>A		intron	N/A	NP_001167567.1
	ZEB1	NM_030751.6		c.259+6791T>A		intron	N/A	NP_110378.3
	ZEB1	NM_001323676.2		c.217+6791T>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.259+6791T>A		intron	N/A	ENSP00000415961.2
	ZEB1	ENST00000320985.14	TSL:1	c.259+6791T>A		intron	N/A	ENSP00000319248.9
	ZEB1	ENST00000558440.5	TSL:1	c.259+6791T>A		intron	N/A	ENSP00000453970.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36932 AN: 151704 Hom.: 10257 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0654

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.196

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.244 AC: 37035 AN: 151822 Hom.: 10312 Cov.: 31 AF XY: 0.240 AC XY: 17836 AN XY: 74166

African (AFR) AF: 0.686 AC: 28416 AN: 41398

American (AMR) AF: 0.113 AC: 1733 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0654 AC: 227 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1027 AN: 5104

South Asian (SAS) AF: 0.157 AC: 754 AN: 4802

European-Finnish (FIN) AF: 0.0720 AC: 760 AN: 10556

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.0538 AC: 3654 AN: 67898

Other (OTH) AF: 0.194 AC: 409 AN: 2112

Alfa AF: 0.150 Hom.: 639

Bravo AF: 0.267

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.20
PhyloP100		-0.62
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: rs220049; hg19: chr10-31756957;