rs1546570

Variant names:

• chr15-66303437-C-A
• rs1546570
• NM_001143688.3:c.294-3387C>A

Variant summary

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

The NM_001143688.3(DIS3L):​c.294-3387C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,102 control chromosomes in the GnomAD database, including 3,254 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 0.20 (3254 hom., cov: 32)
• Consequence: DIS3L NM_001143688.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961
• Publications: 5 publications found

Genes affected

DIS3L (HGNC:28698): (DIS3 like exosome 3'-5' exoribonuclease) The cytoplasmic RNA exosome complex degrades unstable mRNAs and is involved in the regular turnover of other mRNAs. The protein encoded by this gene contains 3'-5' exoribonuclease activity and is a catalytic component of this complex. [provided by RefSeq, May 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143688.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L	NM_001143688.3	MANE Select	c.294-3387C>A		intron	N/A	NP_001137160.1	Q8TF46-1
	DIS3L	NM_001323944.2		c.243-3387C>A		intron	N/A	NP_001310873.1
	DIS3L	NM_001323948.2		c.243-5272C>A		intron	N/A	NP_001310877.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L	ENST00000319212.9	TSL:5 MANE Select	c.294-3387C>A		intron	N/A	ENSP00000321711.4	Q8TF46-1
	DIS3L	ENST00000319194.9	TSL:1	c.45-3387C>A		intron	N/A	ENSP00000321583.5	Q8TF46-4
	DIS3L	ENST00000530537.1	TSL:1	n.45-3460C>A		intron	N/A	ENSP00000432407.1	E9PKI7

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29807 AN: 151984 Hom.: 3248 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0696

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.196 AC: 29839 AN: 152102 Hom.: 3254 Cov.: 32 AF XY: 0.193 AC XY: 14315 AN XY: 74346

African (AFR) AF: 0.133 AC: 5510 AN: 41490

American (AMR) AF: 0.183 AC: 2793 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3470

East Asian (EAS) AF: 0.0698 AC: 361 AN: 5172

South Asian (SAS) AF: 0.126 AC: 607 AN: 4818

European-Finnish (FIN) AF: 0.230 AC: 2434 AN: 10568

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16585 AN: 67996

Other (OTH) AF: 0.204 AC: 431 AN: 2110

Alfa AF: 0.217 Hom.: 677

Bravo AF: 0.192

Asia WGS AF: 0.114 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.32
DANN	Benign	0.58
PhyloP100		-0.96
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: rs1546570; hg19: chr15-66595775;