rs6440082

chr3-142395564-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRN1	NM_001282857.2	c.2339+1765C>T		intron_variant		ENST00000392981.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRN1	ENST00000392981.7	c.2339+1765C>T		intron_variant		1	NM_001282857.2	P3
XRN1	ENST00000264951.8	c.2339+1765C>T		intron_variant		1		A2
XRN1	ENST00000498077.6	c.735+1765C>T		intron_variant		5
XRN1	ENST00000472697.5	n.1930+1765C>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.603

Alfa AF: 0.561 Hom.: 25112

Bravo AF: 0.615

Asia WGS AF: 0.474 AC: 1648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.8
Dann	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs6440082; hg19: chr3-142114406;