rs3757

Positions:

• chr22-20111808-G-A

Variant summary

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

The NM_022720.7(DGCR8):​c.*1700G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 204,996 control chromosomes in the GnomAD database, including 5,275 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 0.21 (3545 hom., cov: 31)
  • Exomes 𝑓: 0.22 (1730 hom.)
• Consequence: DGCR8 NM_022720.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262

Genes affected

DGCR8 (HGNC:2847): (DGCR8 microprocessor complex subunit) This gene encodes a subunit of the microprocessor complex which mediates the biogenesis of microRNAs from the primary microRNA transcript. The encoded protein is a double-stranded RNA binding protein that functions as the non-catalytic subunit of the microprocessor complex. This protein is required for binding the double-stranded RNA substrate and facilitates cleavage of the RNA by the ribonuclease III protein, Drosha. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGCR8	NM_022720.7	c.*1700G>A		3_prime_UTR_variant	14/14	ENST00000351989.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGCR8	ENST00000351989.8	c.*1700G>A		3_prime_UTR_variant	14/14	1	NM_022720.7	P1
	ENST00000412713.1	n.68C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31333 AN: 150656 Hom.: 3545 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.223 AC: 12070 AN: 54224 Hom.: 1730 Cov.: 0 AF XY: 0.224 AC XY: 6070 AN XY: 27090

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.204

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.208 AC: 31341 AN: 150772 Hom.: 3545 Cov.: 31 AF XY: 0.209 AC XY: 15374 AN XY: 73606

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.218

Alfa AF: 0.234 Hom.: 3749

Bravo AF: 0.208

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.3
DANN	Benign	0.78

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: rs3757; hg19: chr22-20099331;