rs11670146

chr19-1847744-G-A

Variant summary

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

The NM_020695.4(REXO1):c.157+458C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,166 control chromosomes in the GnomAD database, including 12,970 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 (12970 hom., cov: 33)
• Consequence: REXO1 NM_020695.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.623

Genes affected

REXO1 (HGNC:24616): (RNA exonuclease 1 homolog) Predicted to enable exonuclease activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REXO1	NM_020695.4	c.157+458C>T		intron_variant		ENST00000170168.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REXO1	ENST00000170168.9	c.157+458C>T		intron_variant		1	NM_020695.4	P2
REXO1	ENST00000587524.1	n.245+458C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57637 AN: 152048 Hom.: 12967 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.379 AC: 57645 AN: 152166 Hom.: 12970 Cov.: 33 AF XY: 0.375 AC XY: 27929 AN XY: 74400

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.422

Alfa AF: 0.439 Hom.: 1994

Bravo AF: 0.366

Asia WGS AF: 0.359 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.2
Dann	Benign	0.76

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: rs11670146; hg19: chr19-1847743;