rs16932309

Positions:

• chr10-31291676-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000605946.1(ZEB1-AS1):​n.177+27839G>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 151,830 control chromosomes in the GnomAD database, including 2,737 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 0.14 (2737 hom., cov: 31)
• Consequence: ZEB1-AS1 ENST00000605946.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB1-AS1	ENST00000605946.1	n.177+27839G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20957 AN: 151712 Hom.: 2720 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0663

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0471

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.138 AC: 21010 AN: 151830 Hom.: 2737 Cov.: 31 AF XY: 0.139 AC XY: 10328 AN XY: 74212

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.0662

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.0853

Gnomad4 FIN AF: 0.0690

Gnomad4 NFE AF: 0.0471

Gnomad4 OTH AF: 0.114

Alfa AF: 0.100 Hom.: 283

Bravo AF: 0.149

Asia WGS AF: 0.118 AC: 409 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.7
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16932309; hg19: chr10-31580605;