3-58205706-G-A

Variant names:

• chr3-58205706-G-A
• rs9311671
• NM_004944.4:c.231-146C>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 10 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 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.231-146C>T		intron	N/A	NP_004935.1
	DNASE1L3	NM_001256560.2		c.231-825C>T		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.231-146C>T		intron	N/A	ENSP00000378053.2
	DNASE1L3	ENST00000483681.5	TSL:5	c.231-146C>T		intron	N/A	ENSP00000417047.1
	DNASE1L3	ENST00000486455.5	TSL:2	c.231-825C>T		intron	N/A	ENSP00000419052.1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53046 AN: 152046 Hom.: 10111 Cov.: 33

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

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

GnomAD4 genome AF: 0.349 AC: 53106 AN: 152164 Hom.: 10124 Cov.: 33 AF XY: 0.358 AC XY: 26658 AN XY: 74386

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: 72 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17748 AN: 67990

Other (OTH) AF: 0.333 AC: 702 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-0.056
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: rs9311671; hg19: chr3-58191433; COSMIC: COSV59156233; COSMIC: COSV59156233;