chr3-142401944-C-T

Position:

• chr3-142401944-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRN1	NM_001282857.2	c.2104-1397G>A		intron_variant		ENST00000392981.7	NP_001269786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRN1	ENST00000392981.7	c.2104-1397G>A		intron_variant		1	NM_001282857.2	ENSP00000376707	P3
XRN1	ENST00000264951.8	c.2104-1397G>A		intron_variant		1		ENSP00000264951	A2
XRN1	ENST00000498077.6	c.500-1397G>A		intron_variant		5		ENSP00000419683
XRN1	ENST00000472697.5	n.1695-1397G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.777

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.600

Alfa AF: 0.557 Hom.: 40204

Bravo AF: 0.610

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.16
DANN	Benign	0.22

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: rs13061823; hg19: chr3-142120786;