rs10485627

chr20-21338339-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012255.5(XRN2):c.1234-705A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 152,204 control chromosomes in the GnomAD database, including 1,298 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 0.078 (1298 hom., cov: 32)
• Consequence: XRN2 NM_012255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110

Genes affected

XRN2 (HGNC:12836): (5'-3' exoribonuclease 2) This gene encodes a 5'-3' exonuclease that promotes transcription termination at cotranscriptional cleavage sites. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRN2	NM_012255.5	c.1234-705A>C		intron_variant		ENST00000377191.5
XRN2	NM_001317960.1	c.1468-705A>C		intron_variant
XRN2	XM_017027722.2	c.1468-705A>C		intron_variant
XRN2	XM_017027723.3	c.-63-681A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRN2	ENST00000377191.5	c.1234-705A>C		intron_variant		1	NM_012255.5	P1

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11851 AN: 152086 Hom.: 1292 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.0965

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.0646

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

GnomAD4 genome AF: 0.0780 AC: 11877 AN: 152204 Hom.: 1298 Cov.: 32 AF XY: 0.0767 AC XY: 5711 AN XY: 74430

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.0278

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.0960

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00113

Gnomad4 OTH AF: 0.0644

Alfa AF: 0.0162 Hom.: 224

Bravo AF: 0.0859

Asia WGS AF: 0.134 AC: 465 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.6
Dann	Benign	0.75

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: rs10485627; hg19: chr20-21318977;