dbSNP rs9311671: DNASE1L3:c.231-146C>T (chr3-58205706-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004944.4(DNASE1L3):c.231-146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 652,636 control chromosomes in the GnomAD database, including 36,658 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 0.35 ( 10124 hom., cov: 33)

Exomes 𝑓: 0.30 ( 26534 hom. )

Consequence

DNASE1L3
NM_004944.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0560

Publications

10 publications found

Variant links:

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

DNASE1L3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNASE1L3	NM_004944.4 link	c.231-146C>T		intron_variant	Intron 2 of 7	ENST00000394549.7	NP_004935.1	Q13609-1A0A024R365
DNASE1L3	NM_001256560.2 link	c.231-825C>T		intron_variant	Intron 2 of 6		NP_001243489.1	Q13609-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNASE1L3	ENST00000394549.7 link	c.231-146C>T		intron_variant	Intron 2 of 7	1	NM_004944.4	ENSP00000378053.2		Q13609-1

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

53046

AN:

152046

Hom.:

10111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.459

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.632

Gnomad SAS

AF:

0.489

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.329

GnomAD4 exome

AF:

0.304

AC:

151947

AN:

500472

Hom.:

26534

AF XY:

0.307

AC XY:

81161

AN XY:

264090

show subpopulations

African (AFR)

AF:

0.461

AC:

6363

AN:

13796

American (AMR)

AF:

0.312

AC:

6879

AN:

22028

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

3626

AN:

15718

East Asian (EAS)

AF:

0.602

AC:

19182

AN:

31886

South Asian (SAS)

AF:

0.419

AC:

19559

AN:

46718

European-Finnish (FIN)

AF:

0.321

AC:

10727

AN:

33452

Middle Eastern (MID)

AF:

0.270

AC:

1013

AN:

3756

European-Non Finnish (NFE)

AF:

0.249

AC:

76153

AN:

305344

Other (OTH)

AF:

0.304

AC:

8445

AN:

27774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

4271

8541

12812

17082

21353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

764

1528

2292

3056

3820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.349

AC:

53106

AN:

152164

Hom.:

10124

Cov.:

AF XY:

0.358

AC XY:

26658

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.459

AC:

19032

AN:

41504

American (AMR)

AF:

0.332

AC:

5087

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

797

AN:

3470

East Asian (EAS)

AF:

0.632

AC:

3272

AN:

5178

South Asian (SAS)

AF:

0.488

AC:

2355

AN:

4826

European-Finnish (FIN)

AF:

0.345

AC:

3648

AN:

10580

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.261

AC:

17748

AN:

67990

Other (OTH)

AF:

0.333

AC:

702

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1746

3491

5237

6982

8728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.285

Hom.:

11400

Bravo

AF:

0.350

Asia WGS

AF:

0.570

AC:

1984

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.1

(source)

DANN

Benign

0.57

PhyloP100

-0.056

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over