3-142413907-T-C

Variant names:

• chr3-142413907-T-C
• rs9867210
• NM_001282857.2:c.1593+228A>G

Variant summary

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

The NM_001282857.2(XRN1):​c.1593+228A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,040 control chromosomes in the GnomAD database, including 11,225 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 (11225 hom., cov: 32)
• Consequence: XRN1 NM_001282857.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 5 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRN1	NM_001282857.2	c.1593+228A>G		intron_variant	Intron 14 of 40	ENST00000392981.7	NP_001269786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRN1	ENST00000392981.7	c.1593+228A>G		intron_variant	Intron 14 of 40	1	NM_001282857.2	ENSP00000376707.2
XRN1	ENST00000264951.8	c.1593+228A>G		intron_variant	Intron 14 of 41	1		ENSP00000264951.4
XRN1	ENST00000465507.1	n.206+228A>G		intron_variant	Intron 1 of 1	3
XRN1	ENST00000472697.5	n.1184+228A>G		intron_variant	Intron 11 of 20	2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58304 AN: 151922 Hom.: 11213 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.384 AC: 58336 AN: 152040 Hom.: 11225 Cov.: 32 AF XY: 0.383 AC XY: 28441 AN XY: 74332

African (AFR) AF: 0.316 AC: 13089 AN: 41460

American (AMR) AF: 0.381 AC: 5821 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1540 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1888 AN: 5174

South Asian (SAS) AF: 0.307 AC: 1480 AN: 4824

European-Finnish (FIN) AF: 0.404 AC: 4266 AN: 10556

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28731 AN: 67972

Other (OTH) AF: 0.406 AC: 856 AN: 2106

Alfa AF: 0.404 Hom.: 6447

Bravo AF: 0.381

Asia WGS AF: 0.348 AC: 1206 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.3
DANN	Benign	0.70
PhyloP100		-0.0010
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: rs9867210; hg19: chr3-142132749; COSMIC: COSV53820414; COSMIC: COSV53820414;