chr1-84411048-T-G

Position:

• chr1-84411048-T-G

Variant summary

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

The NM_021233.3(DNASE2B):​c.547+49T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 1,528,906 control chromosomes in the GnomAD database, including 217,204 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 (21284 hom., cov: 32)
  • Exomes 𝑓: 0.53 (195920 hom.)
• Consequence: DNASE2B NM_021233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNASE2B	NM_021233.3	c.547+49T>G		intron_variant		ENST00000370665.4	NP_067056.2
DNASE2B	NM_058248.2	c.-78+49T>G		intron_variant			NP_490649.1
DNASE2B	XM_047426625.1	c.310+49T>G		intron_variant			XP_047282581.1
DNASE2B	XM_011541878.3	c.-78+38T>G		intron_variant			XP_011540180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNASE2B	ENST00000370665.4	c.547+49T>G		intron_variant		1	NM_021233.3	ENSP00000359699.3
DNASE2B	ENST00000370662.3	c.-78+49T>G		intron_variant		1		ENSP00000359696.3

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80291 AN: 151804 Hom.: 21265 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.524

GnomAD3 exomes AF: 0.537 AC: 90834 AN: 169138 Hom.: 24681 AF XY: 0.534 AC XY: 47907 AN XY: 89674

Gnomad AFR exome AF: 0.526

Gnomad AMR exome AF: 0.625

Gnomad ASJ exome AF: 0.441

Gnomad EAS exome AF: 0.600

Gnomad SAS exome AF: 0.534

Gnomad FIN exome AF: 0.489

Gnomad NFE exome AF: 0.523

Gnomad OTH exome AF: 0.510

GnomAD4 exome AF: 0.531 AC: 731272 AN: 1376984 Hom.: 195920 Cov.: 23 AF XY: 0.531 AC XY: 362271 AN XY: 682472

Gnomad4 AFR exome AF: 0.523

Gnomad4 AMR exome AF: 0.617

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.621

Gnomad4 SAS exome AF: 0.540

Gnomad4 FIN exome AF: 0.497

Gnomad4 NFE exome AF: 0.529

Gnomad4 OTH exome AF: 0.529

GnomAD4 genome AF: 0.529 AC: 80358 AN: 151922 Hom.: 21284 Cov.: 32 AF XY: 0.528 AC XY: 39167 AN XY: 74226

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.522

Alfa AF: 0.530 Hom.: 4785

Bravo AF: 0.532

Asia WGS AF: 0.590 AC: 2051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.37

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: rs1506700; hg19: chr1-84876731;