20-49286239-T-C

Position:

• chr20-49286239-T-C

Variant summary

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

The NR_003604.3(ZFAS1):​n.793-2806T>C 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 0.668 in 150,828 control chromosomes in the GnomAD database, including 34,603 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 0.67 (34603 hom., cov: 25)
• Consequence: ZFAS1 NR_003604.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

Genes affected

ZFAS1 (HGNC:33101): (ZNFX1 antisense RNA 1) This gene represents a snoRNA host gene that produces a non-coding RNA. Increased expression or amplification of this locus is associated with cancer progression and metastasis. This transcript regulates expression of genes involved in differentiation. It may act a molecular sponge for microRNAs. Alternatively spliced transcript variants have been observed. [provided by RefSeq, Dec 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAS1	NR_003604.3	n.793-2806T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFAS1	ENST00000620594.2	n.328+5275T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.668 AC: 100689 AN: 150710 Hom.: 34593 Cov.: 25

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.668 AC: 100729 AN: 150828 Hom.: 34603 Cov.: 25 AF XY: 0.664 AC XY: 48837 AN XY: 73588

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.789

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.666

Alfa AF: 0.702 Hom.: 13263

Bravo AF: 0.647

Asia WGS AF: 0.545 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.36
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		2.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs237744; hg19: chr20-47902776;