3-142401944-C-T

Variant names:

• chr3-142401944-C-T
• rs13061823
• NM_001282857.2:c.2104-1397G>A

Variant summary

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

The NM_001282857.2(XRN1):​c.2104-1397G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,968 control chromosomes in the GnomAD database, including 28,679 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 0.60 (28679 hom., cov: 31)
• Consequence: XRN1 NM_001282857.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 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.2104-1397G>A		intron	N/A	NP_001269786.1	Q8IZH2-2
	XRN1	NM_019001.5		c.2104-1397G>A		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.2104-1397G>A		intron	N/A	ENSP00000376707.2	Q8IZH2-2
	XRN1	ENST00000264951.8	TSL:1	c.2104-1397G>A		intron	N/A	ENSP00000264951.4	Q8IZH2-1
	XRN1	ENST00000941075.1		c.2104-1397G>A		intron	N/A	ENSP00000611134.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91632 AN: 151848 Hom.: 28646 Cov.: 31

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.603 AC: 91709 AN: 151968 Hom.: 28679 Cov.: 31 AF XY: 0.597 AC XY: 44369 AN XY: 74276

African (AFR) AF: 0.777 AC: 32185 AN: 41446

American (AMR) AF: 0.514 AC: 7845 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1790 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2403 AN: 5170

South Asian (SAS) AF: 0.405 AC: 1954 AN: 4820

European-Finnish (FIN) AF: 0.538 AC: 5666 AN: 10536

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.557 AC: 37817 AN: 67934

Other (OTH) AF: 0.600 AC: 1269 AN: 2114

Alfa AF: 0.570 Hom.: 72350

Bravo AF: 0.610

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.16
DANN	Benign	0.22
PhyloP100		-0.92
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: rs13061823; hg19: chr3-142120786;