rs9867210

Positions:

• chr3-142413907-T-C

Variant summary

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

The NM_001282857.2(XRN1):​c.1593+228A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,040 control chromosomes in the GnomAD database, including 11,225 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 0.38 (11225 hom., cov: 32)
• Consequence: XRN1 NM_001282857.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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]

XRN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRN1	NM_001282857.2	c.1593+228A>G		intron_variant		ENST00000392981.7	NP_001269786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRN1	ENST00000392981.7	c.1593+228A>G		intron_variant		1	NM_001282857.2	ENSP00000376707.2
XRN1	ENST00000264951.8	c.1593+228A>G		intron_variant		1		ENSP00000264951.4
XRN1	ENST00000465507.1	n.206+228A>G		intron_variant		3
XRN1	ENST00000472697.5	n.1184+228A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58304 AN: 151922 Hom.: 11213 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.384 AC: 58336 AN: 152040 Hom.: 11225 Cov.: 32 AF XY: 0.383 AC XY: 28441 AN XY: 74332

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.406

Alfa AF: 0.402 Hom.: 5788

Bravo AF: 0.381

Asia WGS AF: 0.348 AC: 1206 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.3
DANN	Benign	0.70

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: rs9867210; hg19: chr3-142132749; COSMIC: COSV53820414; COSMIC: COSV53820414;