1-84411048-T-G

Variant names:

• chr1-84411048-T-G
• rs1506700
• NM_021233.3:c.547+49T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DNASE2B	NM_021233.3	c.547+49T>G		intron_variant	Intron 4 of 5	ENST00000370665.4	NP_067056.2
DNASE2B	NM_058248.2	c.-78+49T>G		intron_variant	Intron 2 of 3		NP_490649.1
DNASE2B	XM_047426625.1	c.310+49T>G		intron_variant	Intron 3 of 4		XP_047282581.1
DNASE2B	XM_011541878.3	c.-78+38T>G		intron_variant	Intron 1 of 2		XP_011540180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNASE2B	ENST00000370665.4	c.547+49T>G		intron_variant	Intron 4 of 5	1	NM_021233.3	ENSP00000359699.3
DNASE2B	ENST00000370662.3	c.-78+49T>G		intron_variant	Intron 2 of 3	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

GnomAD2 exomes AF: 0.537 AC: 90834 AN: 169138 AF XY: 0.534

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 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

African (AFR) AF: 0.523 AC: 16287 AN: 31118

American (AMR) AF: 0.617 AC: 21832 AN: 35360

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 10797 AN: 25034

East Asian (EAS) AF: 0.621 AC: 22840 AN: 36790

South Asian (SAS) AF: 0.540 AC: 42535 AN: 78776

European-Finnish (FIN) AF: 0.497 AC: 24572 AN: 49460

Middle Eastern (MID) AF: 0.485 AC: 2736 AN: 5644

European-Non Finnish (NFE) AF: 0.529 AC: 559267 AN: 1057338

Other (OTH) AF: 0.529 AC: 30406 AN: 57464

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

African (AFR) AF: 0.526 AC: 21755 AN: 41398

American (AMR) AF: 0.564 AC: 8614 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1483 AN: 3468

East Asian (EAS) AF: 0.611 AC: 3157 AN: 5164

South Asian (SAS) AF: 0.545 AC: 2620 AN: 4806

European-Finnish (FIN) AF: 0.475 AC: 5011 AN: 10544

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36041 AN: 67946

Other (OTH) AF: 0.522 AC: 1104 AN: 2114

Alfa AF: 0.532 Hom.: 7932

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
PhyloP100		0.058
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1506700; hg19: chr1-84876731; COSMIC: COSV107473353;