rs9311671

Positions:

• chr3-58205706-G-A
• chr3-58205706-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DNASE1L3	NM_004944.4	c.231-146C>T		intron_variant		ENST00000394549.7	NP_004935.1
DNASE1L3	NM_001256560.2	c.231-825C>T		intron_variant			NP_001243489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNASE1L3	ENST00000394549.7	c.231-146C>T		intron_variant		1	NM_004944.4	ENSP00000378053	P1

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

Gnomad4 AFR exome AF: 0.461

Gnomad4 AMR exome AF: 0.312

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.602

Gnomad4 SAS exome AF: 0.419

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.304

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

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.333

Alfa AF: 0.280 Hom.: 8647

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
DANN	Benign	0.57

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: rs9311671; hg19: chr3-58191433; COSMIC: COSV59156233; COSMIC: COSV59156233;