rs11670146

Variant names:

• chr19-1847744-G-A
• rs11670146
• NM_020695.4:c.157+458C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
REXO1	NM_020695.4	c.157+458C>T		intron_variant	Intron 1 of 15	ENST00000170168.9	NP_065746.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REXO1	ENST00000170168.9	c.157+458C>T		intron_variant	Intron 1 of 15	1	NM_020695.4	ENSP00000170168.3
REXO1	ENST00000587524.1	n.245+458C>T		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.139 AC: 5793 AN: 41544

American (AMR) AF: 0.366 AC: 5597 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1623 AN: 3468

East Asian (EAS) AF: 0.266 AC: 1373 AN: 5170

South Asian (SAS) AF: 0.414 AC: 1999 AN: 4832

European-Finnish (FIN) AF: 0.412 AC: 4360 AN: 10586

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35520 AN: 67956

Other (OTH) AF: 0.422 AC: 891 AN: 2110

Alfa AF: 0.427 Hom.: 2001

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
PhyloP100		0.62
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: rs11670146; hg19: chr19-1847743;