rs732982

Variant names:

• chr18-57060228-G-A
• rs732982
• ENST00000553704.3:n.411-2228C>T

Variant summary

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

The ENST00000553704.3(LINC-ROR):​n.411-2228C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,088 control chromosomes in the GnomAD database, including 6,364 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 (6364 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: LINC-ROR ENST00000553704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16
• Publications: 3 publications found

Genes affected

LINC-ROR (HGNC:43773): (long intergenic non-protein coding RNA, regulator of reprogramming) This gene produces a long non-coding RNA that regulates the reprogramming of pluripotent stem cells. This RNA suppresses induction of tumor protein p53 after DNA damage. It is thought to act as a sponge for microRNAs that regulate stem cell factors POU class 5 homeobox 1, Nanog, and SRY-box 2. This RNA may also have a extracellular role in modulating response to hypoxia in hepatocellular cancer cells. Expression of this transcript is associated with tumor progression and epithelial to mesenchymal transition and metastasis. [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=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000553704.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC-ROR	NR_048536.2		n.411-2228C>T		intron	N/A
	LINC-ROR	NR_152602.1		n.411-3542C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC-ROR	ENST00000553704.3	TSL:1	n.411-2228C>T		intron	N/A
	LINC-ROR	ENST00000642403.1		n.358+125C>T		intron	N/A
	LINC-ROR	ENST00000644118.1		n.195-1478C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39251 AN: 151970 Hom.: 6361 Cov.: 33

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.0457

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.258 AC: 39243 AN: 152088 Hom.: 6364 Cov.: 33 AF XY: 0.254 AC XY: 18877 AN XY: 74332

African (AFR) AF: 0.0837 AC: 3472 AN: 41494

American (AMR) AF: 0.212 AC: 3244 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1166 AN: 3468

East Asian (EAS) AF: 0.0456 AC: 236 AN: 5178

South Asian (SAS) AF: 0.272 AC: 1310 AN: 4810

European-Finnish (FIN) AF: 0.355 AC: 3749 AN: 10558

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25093 AN: 67980

Other (OTH) AF: 0.274 AC: 580 AN: 2114

Alfa AF: 0.315 Hom.: 3098

Bravo AF: 0.238

Asia WGS AF: 0.168 AC: 583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.82
PhyloP100		3.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs732982;

hg19: chr18-54727459;