3-58209647-A-G

Variant names:

• chr3-58209647-A-G
• rs1878014
• NM_004944.4:c.141+1119T>C

Variant summary

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

The NM_004944.4(DNASE1L3):​c.141+1119T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,092 control chromosomes in the GnomAD database, including 6,694 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 0.28 (6694 hom., cov: 32)
• Consequence: DNASE1L3 NM_004944.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 5 publications found

Genes affected

DNASE1L3 (HGNC:2959): (deoxyribonuclease 1 like 3) This gene encodes a member of the deoxyribonuclease I family. The encoded protein hydrolyzes DNA, is not inhibited by actin, and mediates the breakdown of DNA during apoptosis. Mutations in this gene are a cause of systemic lupus erythematosus-16. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

DNASE1L3 Gene-Disease associations (from GenCC):

• autosomal systemic lupus erythematosus type 16

  Inheritance: AR, AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• hypocomplementemic urticarial vasculitis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004944.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNASE1L3	NM_004944.4	MANE Select	c.141+1119T>C		intron	N/A	NP_004935.1
	DNASE1L3	NM_001256560.2		c.141+1119T>C		intron	N/A	NP_001243489.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNASE1L3	ENST00000394549.7	TSL:1 MANE Select	c.141+1119T>C		intron	N/A	ENSP00000378053.2
	DNASE1L3	ENST00000483681.5	TSL:5	c.141+1119T>C		intron	N/A	ENSP00000417047.1
	DNASE1L3	ENST00000486455.5	TSL:2	c.141+1119T>C		intron	N/A	ENSP00000419052.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43059 AN: 151976 Hom.: 6688 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.283 AC: 43086 AN: 152092 Hom.: 6694 Cov.: 32 AF XY: 0.295 AC XY: 21933 AN XY: 74354

African (AFR) AF: 0.233 AC: 9691 AN: 41510

American (AMR) AF: 0.303 AC: 4634 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3468

East Asian (EAS) AF: 0.630 AC: 3251 AN: 5160

South Asian (SAS) AF: 0.484 AC: 2330 AN: 4818

European-Finnish (FIN) AF: 0.345 AC: 3646 AN: 10570

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17638 AN: 67974

Other (OTH) AF: 0.282 AC: 596 AN: 2114

Alfa AF: 0.271 Hom.: 2216

Bravo AF: 0.274

Asia WGS AF: 0.546 AC: 1899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.47
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1878014; hg19: chr3-58195374;