chr3-142387509-T-A

Variant names:

• chr3-142387509-T-A
• rs9859834
• NM_001282857.2:c.2340-2824A>T

Variant summary

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

The NM_001282857.2(XRN1):​c.2340-2824A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,986 control chromosomes in the GnomAD database, including 17,723 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 0.47 (17723 hom., cov: 31)
• Consequence: XRN1 NM_001282857.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.870
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRN1	NM_001282857.2	c.2340-2824A>T		intron_variant	Intron 20 of 40	ENST00000392981.7	NP_001269786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRN1	ENST00000392981.7	c.2340-2824A>T		intron_variant	Intron 20 of 40	1	NM_001282857.2	ENSP00000376707.2
XRN1	ENST00000264951.8	c.2340-2824A>T		intron_variant	Intron 20 of 41	1		ENSP00000264951.4
XRN1	ENST00000498077.6	c.735-2824A>T		intron_variant	Intron 6 of 26	5		ENSP00000419683.2
XRN1	ENST00000472697.5	n.1931-2824A>T		intron_variant	Intron 17 of 20	2

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71763 AN: 151868 Hom.: 17700 Cov.: 31

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.473 AC: 71828 AN: 151986 Hom.: 17723 Cov.: 31 AF XY: 0.468 AC XY: 34797 AN XY: 74302

African (AFR) AF: 0.634 AC: 26279 AN: 41446

American (AMR) AF: 0.416 AC: 6355 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1522 AN: 3466

East Asian (EAS) AF: 0.365 AC: 1891 AN: 5174

South Asian (SAS) AF: 0.309 AC: 1492 AN: 4824

European-Finnish (FIN) AF: 0.401 AC: 4232 AN: 10550

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28414 AN: 67944

Other (OTH) AF: 0.469 AC: 988 AN: 2108

Alfa AF: 0.453 Hom.: 2019

Bravo AF: 0.484

Asia WGS AF: 0.371 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.88
DANN	Benign	0.29
PhyloP100		-0.87
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: rs9859834; hg19: chr3-142106351;