20-49286239-T-C

Variant names:

• chr20-49286239-T-C
• rs237744
• ENST00000326677.10:n.329-2806T>C

Variant summary

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

The ENST00000326677.10(ZFAS1):​n.329-2806T>C variant causes a intron 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 ENST00000326677.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZFAS1	NR_003604.3	n.793-2806T>C		intron_variant	Intron 4 of 4
ZFAS1	NR_003605.2	n.474-2806T>C		intron_variant	Intron 4 of 4
ZFAS1	NR_003606.3	n.645-2806T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAS1	ENST00000326677.10	n.329-2806T>C		intron_variant	Intron 3 of 3	1
ZFAS1	ENST00000371743.8	n.793-2806T>C		intron_variant	Intron 4 of 4	1
ZFAS1	ENST00000417721.6	n.645-2806T>C		intron_variant	Intron 2 of 2	1

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

African (AFR) AF: 0.528 AC: 21631 AN: 40932

American (AMR) AF: 0.604 AC: 9137 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2730 AN: 3462

East Asian (EAS) AF: 0.503 AC: 2565 AN: 5100

South Asian (SAS) AF: 0.549 AC: 2609 AN: 4754

European-Finnish (FIN) AF: 0.791 AC: 8209 AN: 10384

Middle Eastern (MID) AF: 0.743 AC: 217 AN: 292

European-Non Finnish (NFE) AF: 0.761 AC: 51539 AN: 67768

Other (OTH) AF: 0.666 AC: 1396 AN: 2096

Alfa AF: 0.706 Hom.: 21706

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
PhyloP100		0.26
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

Other links and lift over

dbSNP: rs237744; hg19: chr20-47902776;