3-142395852-C-T

Variant names:

• chr3-142395852-C-T
• rs7643377
• NM_001282857.2:c.2339+1477G>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.2339+1477G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,042 control chromosomes in the GnomAD database, including 10,797 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 (10797 hom., cov: 32)
• Consequence: XRN1 NM_001282857.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409
• Publications: 8 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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 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+1477G>A		intron	N/A	NP_001269786.1	Q8IZH2-2
	XRN1	NM_019001.5		c.2339+1477G>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.2339+1477G>A		intron	N/A	ENSP00000376707.2	Q8IZH2-2
	XRN1	ENST00000264951.8	TSL:1	c.2339+1477G>A		intron	N/A	ENSP00000264951.4	Q8IZH2-1
	XRN1	ENST00000941075.1		c.2339+1477G>A		intron	N/A	ENSP00000611134.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57202 AN: 151922 Hom.: 10783 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.376 AC: 57236 AN: 152042 Hom.: 10797 Cov.: 32 AF XY: 0.375 AC XY: 27905 AN XY: 74318

African (AFR) AF: 0.313 AC: 12992 AN: 41470

American (AMR) AF: 0.378 AC: 5776 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1525 AN: 3470

East Asian (EAS) AF: 0.364 AC: 1883 AN: 5176

South Asian (SAS) AF: 0.307 AC: 1481 AN: 4828

European-Finnish (FIN) AF: 0.390 AC: 4114 AN: 10550

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27966 AN: 67964

Other (OTH) AF: 0.403 AC: 851 AN: 2110

Alfa AF: 0.395 Hom.: 6264

Bravo AF: 0.375

Asia WGS AF: 0.346 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.8
DANN	Benign	0.67
PhyloP100		0.41
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: rs7643377; hg19: chr3-142114694;