rs1351965

Positions:

• chr3-142404542-A-G

Variant summary

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

The NM_001282857.2(XRN1):​c.1883+365T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,110 control chromosomes in the GnomAD database, including 43,683 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 0.75 (43683 hom., cov: 31)
• Consequence: XRN1 NM_001282857.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRN1	NM_001282857.2	c.1883+365T>C		intron_variant		ENST00000392981.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRN1	ENST00000392981.7	c.1883+365T>C		intron_variant		1	NM_001282857.2	P3
XRN1	ENST00000264951.8	c.1883+365T>C		intron_variant		1		A2
XRN1	ENST00000498077.6	c.279+365T>C		intron_variant		5
XRN1	ENST00000472697.5	n.1474+365T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113745 AN: 151992 Hom.: 43620 Cov.: 31

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.749 AC: 113864 AN: 152110 Hom.: 43683 Cov.: 31 AF XY: 0.747 AC XY: 55516 AN XY: 74342

Gnomad4 AFR AF: 0.921

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.751

Alfa AF: 0.693 Hom.: 35260

Bravo AF: 0.762

Asia WGS AF: 0.597 AC: 2076 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.9
DANN	Benign	0.47

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: rs1351965; hg19: chr3-142123384;