rs1546570

Positions:

• chr15-66303437-C-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIS3L	NM_001143688.3	c.294-3387C>A		intron_variant		ENST00000319212.9	NP_001137160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIS3L	ENST00000319212.9	c.294-3387C>A		intron_variant		5	NM_001143688.3	ENSP00000321711	P1

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

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.0698

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.204

Alfa AF: 0.219 Hom.: 671

Bravo AF: 0.192

Asia WGS AF: 0.114 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.32
DANN	Benign	0.58

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: rs1546570; hg19: chr15-66595775;