1-84403278-T-C

Position:

• chr1-84403278-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.303+1200T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.947 in 152,280 control chromosomes in the GnomAD database, including 68,362 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 0.95 (68362 hom., cov: 32)
• Consequence: DNASE2B NM_021233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634

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 = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNASE2B	NM_021233.3	c.303+1200T>C		intron_variant		ENST00000370665.4	NP_067056.2
DNASE2B	XM_047426625.1	c.66+1200T>C		intron_variant			XP_047282581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNASE2B	ENST00000370665.4	c.303+1200T>C		intron_variant		1	NM_021233.3	ENSP00000359699.3

Frequencies

GnomAD3 genomes AF: 0.947 AC: 144057 AN: 152162 Hom.: 68316 Cov.: 32

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.959

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

GnomAD4 genome AF: 0.947 AC: 144161 AN: 152280 Hom.: 68362 Cov.: 32 AF XY: 0.948 AC XY: 70558 AN XY: 74460

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.974

Gnomad4 ASJ AF: 0.977

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.988

Gnomad4 FIN AF: 0.951

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.960

Alfa AF: 0.945 Hom.: 9954

Bravo AF: 0.946

Asia WGS AF: 0.990 AC: 3442 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.6
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs604708; hg19: chr1-84868961;