rs12144715

Positions:

• chr1-84399547-A-T

Variant summary

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

The NM_021233.3(DNASE2B):​c.125+858A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 152,276 control chromosomes in the GnomAD database, including 591 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 0.079 (591 hom., cov: 32)
• Consequence: DNASE2B NM_021233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.792

Genes affected

DNASE2B (HGNC:28875): (deoxyribonuclease 2 beta) The protein encoded by this gene shares considerable sequence similarity to, and is structurally related to DNase II. The latter is a well characterized endonuclease that catalyzes DNA hydrolysis in the absence of divalent cations at acidic pH. Unlike DNase II which is ubiquitously expressed, expression of this gene product is restricted to the salivary gland and lungs. The gene has been localized to chromosome 1p22.3 adjacent (and in opposite orientation) to the uricase pseudogene. Two transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNASE2B	NM_021233.3	c.125+858A>T		intron_variant		ENST00000370665.4	NP_067056.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNASE2B	ENST00000370665.4	c.125+858A>T		intron_variant		1	NM_021233.3	ENSP00000359699.3

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 11938 AN: 152158 Hom.: 585 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0904

Gnomad ASJ AF: 0.0940

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.0945

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0576

Gnomad OTH AF: 0.0775

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0786 AC: 11963 AN: 152276 Hom.: 591 Cov.: 32 AF XY: 0.0781 AC XY: 5815 AN XY: 74454

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0904

Gnomad4 ASJ AF: 0.0940

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.0946

Gnomad4 FIN AF: 0.0215

Gnomad4 NFE AF: 0.0576

Gnomad4 OTH AF: 0.0767

Alfa AF: 0.0609 Hom.: 172

Bravo AF: 0.0852

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12144715; hg19: chr1-84865230;