10-31265249-C-T

Variant names:

• chr10-31265249-C-T
• rs7083727
• ENST00000605946.1:n.177+54266G>A

Variant summary

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

The ENST00000605946.1(ZEB1-AS1):​n.177+54266G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,842 control chromosomes in the GnomAD database, including 6,721 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 0.26 (6721 hom., cov: 30)
• Consequence: ZEB1-AS1 ENST00000605946.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98
• Publications: 1 publications found

Genes affected

ZEB1-AS1 (HGNC:42354): (ZEB1 antisense RNA 1) This locus produces long non-coding RNA that is transcribed from a shared bi-directional promoter with zinc finger E-box binding homeobox 1 (ZEB1). This transcript binds lysine methyltransferase 2A and promotes histone modifications that are thought to promote expression of ZEB1. Expression of this gene is correlated with tumor progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZEB1-AS1	ENST00000605946.1	n.177+54266G>A		intron_variant	Intron 1 of 1	5
ZEB1-AS1	ENST00000805106.1	n.202+55034G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39549 AN: 151724 Hom.: 6714 Cov.: 30

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.0344

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.261 AC: 39557 AN: 151842 Hom.: 6721 Cov.: 30 AF XY: 0.254 AC XY: 18828 AN XY: 74170

African (AFR) AF: 0.0696 AC: 2886 AN: 41460

American (AMR) AF: 0.252 AC: 3842 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3468

East Asian (EAS) AF: 0.0345 AC: 178 AN: 5156

South Asian (SAS) AF: 0.216 AC: 1041 AN: 4810

European-Finnish (FIN) AF: 0.297 AC: 3113 AN: 10496

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 25986 AN: 67896

Other (OTH) AF: 0.290 AC: 607 AN: 2094

Alfa AF: 0.321 Hom.: 8242

Bravo AF: 0.250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.048
DANN	Benign	0.26
PhyloP100		-3.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7083727; hg19: chr10-31554178;