rs3121147

Positions:

• chr1-84411300-T-C

Variant summary

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

The NM_021233.3(DNASE2B):​c.547+301T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,818 control chromosomes in the GnomAD database, including 21,386 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 0.53 (21386 hom., cov: 30)
• Consequence: DNASE2B NM_021233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNASE2B	NM_021233.3	c.547+301T>C		intron_variant		ENST00000370665.4
DNASE2B	NM_058248.2	c.-78+301T>C		intron_variant
DNASE2B	XM_011541878.3	c.-78+290T>C		intron_variant
DNASE2B	XM_047426625.1	c.310+301T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNASE2B	ENST00000370665.4	c.547+301T>C		intron_variant		1	NM_021233.3	P1
DNASE2B	ENST00000370662.3	c.-78+301T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80438 AN: 151698 Hom.: 21362 Cov.: 30

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.530 AC: 80512 AN: 151818 Hom.: 21386 Cov.: 30 AF XY: 0.529 AC XY: 39257 AN XY: 74198

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.522

Alfa AF: 0.531 Hom.: 9926

Bravo AF: 0.534

Asia WGS AF: 0.589 AC: 2050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.31
DANN	Benign	0.55

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: rs3121147; hg19: chr1-84876983;