rs6440082

Variant names:

• chr3-142395564-G-A
• rs6440082
• NM_001282857.2:c.2339+1765C>T

Variant summary

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

The NM_001282857.2(XRN1):​c.2339+1765C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,018 control chromosomes in the GnomAD database, including 29,265 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 0.61 (29265 hom., cov: 31)
• Consequence: XRN1 NM_001282857.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 2 publications found

Genes affected

XRN1 (HGNC:30654): (5'-3' exoribonuclease 1) This gene encodes a member of the 5'-3' exonuclease family. The encoded protein may be involved in replication-dependent histone mRNA degradation, and interacts directly with the enhancer of mRNA-decapping protein 4. In addition to mRNA metabolism, a similar protein in yeast has been implicated in a variety of nuclear and cytoplasmic functions, including homologous recombination, meiosis, telomere maintenance, and microtubule assembly. Mutations in this gene are associated with osteosarcoma, suggesting that the encoded protein may also play a role in bone formation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282857.2. 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
	XRN1	NM_001282857.2	MANE Select	c.2339+1765C>T		intron	N/A	NP_001269786.1	Q8IZH2-2
	XRN1	NM_019001.5		c.2339+1765C>T		intron	N/A	NP_061874.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRN1	ENST00000392981.7	TSL:1 MANE Select	c.2339+1765C>T		intron	N/A	ENSP00000376707.2	Q8IZH2-2
	XRN1	ENST00000264951.8	TSL:1	c.2339+1765C>T		intron	N/A	ENSP00000264951.4	Q8IZH2-1
	XRN1	ENST00000941075.1		c.2339+1765C>T		intron	N/A	ENSP00000611134.1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92224 AN: 151900 Hom.: 29208 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.607 AC: 92331 AN: 152018 Hom.: 29265 Cov.: 31 AF XY: 0.601 AC XY: 44668 AN XY: 74292

African (AFR) AF: 0.802 AC: 33254 AN: 41482

American (AMR) AF: 0.514 AC: 7855 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1788 AN: 3468

East Asian (EAS) AF: 0.464 AC: 2392 AN: 5158

South Asian (SAS) AF: 0.406 AC: 1951 AN: 4810

European-Finnish (FIN) AF: 0.528 AC: 5561 AN: 10538

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.551 AC: 37478 AN: 67970

Other (OTH) AF: 0.603 AC: 1273 AN: 2112

Alfa AF: 0.568 Hom.: 33337

Bravo AF: 0.615

Asia WGS AF: 0.474 AC: 1648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.27
PhyloP100		-0.023
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6440082; hg19: chr3-142114406;