rs3732630

Variant names:

• chr3-58193301-T-C
• rs3732630
• NM_004944.4:c.801+42A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-58193301-T-C
• chr3-58193301-T-A
• chr3-58193301-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004944.4(DNASE1L3):​c.801+42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,603,380 control chromosomes in the GnomAD database, including 96,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8368 hom., cov: 30)
  • Exomes 𝑓: 0.34 (88454 hom.)
• Consequence: DNASE1L3 NM_004944.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.635
• Publications: 16 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: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• hypocomplementemic urticarial vasculitis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-58193301-T-C is Benign according to our data. Variant chr3-58193301-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688407.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNASE1L3	NM_004944.4	MANE Select	c.801+42A>G		intron	N/A	NP_004935.1	Q13609-1
	DNASE1L3	NM_001256560.2		c.711+42A>G		intron	N/A	NP_001243489.1	Q13609-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNASE1L3	ENST00000394549.7	TSL:1 MANE Select	c.801+42A>G		intron	N/A	ENSP00000378053.2	Q13609-1
	DNASE1L3	ENST00000483681.5	TSL:5	c.843A>G	p.Lys281Lys	synonymous	Exon 9 of 9	ENSP00000417047.1	A0A0A0MT68
	DNASE1L3	ENST00000907344.1		c.828+42A>G		intron	N/A	ENSP00000577403.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48257 AN: 151818 Hom.: 8372 Cov.: 30

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.287

GnomAD2 exomes AF: 0.366 AC: 91426 AN: 250000 AF XY: 0.367

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.401

Gnomad ASJ exome AF: 0.219

Gnomad EAS exome AF: 0.645

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.319

Gnomad OTH exome AF: 0.333

GnomAD4 exome AF: 0.342 AC: 496325 AN: 1451446 Hom.: 88454 Cov.: 28 AF XY: 0.344 AC XY: 248376 AN XY: 722674

African (AFR) AF: 0.229 AC: 7627 AN: 33280

American (AMR) AF: 0.396 AC: 17642 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 5700 AN: 26060

East Asian (EAS) AF: 0.613 AC: 24292 AN: 39622

South Asian (SAS) AF: 0.460 AC: 39531 AN: 85934

European-Finnish (FIN) AF: 0.344 AC: 18296 AN: 53148

Middle Eastern (MID) AF: 0.230 AC: 1321 AN: 5750

European-Non Finnish (NFE) AF: 0.328 AC: 361591 AN: 1103058

Other (OTH) AF: 0.339 AC: 20325 AN: 60004

GnomAD4 genome AF: 0.318 AC: 48274 AN: 151934 Hom.: 8368 Cov.: 30 AF XY: 0.325 AC XY: 24139 AN XY: 74240

African (AFR) AF: 0.237 AC: 9841 AN: 41436

American (AMR) AF: 0.362 AC: 5523 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3464

East Asian (EAS) AF: 0.633 AC: 3273 AN: 5168

South Asian (SAS) AF: 0.497 AC: 2387 AN: 4802

European-Finnish (FIN) AF: 0.350 AC: 3685 AN: 10534

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21687 AN: 67940

Other (OTH) AF: 0.291 AC: 615 AN: 2110

Alfa AF: 0.315 Hom.: 21943

Bravo AF: 0.313

Asia WGS AF: 0.549 AC: 1908 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.76
DANN	Benign	0.52
PhyloP100		-0.64
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: rs3732630; hg19: chr3-58179028; COSMIC: COSV59155459;