3-58209647-A-G

Position:

• chr3-58209647-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000394549.7(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 ENST00000394549.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNASE1L3	NM_004944.4	c.141+1119T>C		intron_variant		ENST00000394549.7	NP_004935.1
DNASE1L3	NM_001256560.2	c.141+1119T>C		intron_variant			NP_001243489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNASE1L3	ENST00000394549.7	c.141+1119T>C		intron_variant		1	NM_004944.4	ENSP00000378053	P1

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

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.282

Alfa AF: 0.273 Hom.: 1398

Bravo AF: 0.274

Asia WGS AF: 0.546 AC: 1899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs1878014; hg19: chr3-58195374;