rs720014

chr22-20111359-T-Cchr22-20111359-T-G

Variant summary

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

The NM_022720.7(DGCR8):c.*1251T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 388,090 control chromosomes in the GnomAD database, including 10,780 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 0.22 (3595 hom., cov: 31)
  • Exomes 𝑓: 0.24 (7185 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 = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGCR8	NM_022720.7	c.*1251T>C		3_prime_UTR_variant	14/14	ENST00000351989.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGCR8	ENST00000351989.8	c.*1251T>C		3_prime_UTR_variant	14/14	1	NM_022720.7	P1
	ENST00000412713.1	n.88-100A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.221 AC: 31268 AN: 141644 Hom.: 3597 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.324

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.238 AC: 58698 AN: 246394 Hom.: 7185 Cov.: 0 AF XY: 0.239 AC XY: 29790 AN XY: 124874

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.298

Gnomad4 EAS exome AF: 0.252

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.221 AC: 31260 AN: 141696 Hom.: 3595 Cov.: 31 AF XY: 0.223 AC XY: 15293 AN XY: 68604

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.241

Alfa AF: 0.236 Hom.: 2364

Bravo AF: 0.209

Asia WGS AF: 0.148 AC: 506 AN: 3416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.8
Dann	Benign	0.67

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: rs720014; hg19: chr22-20098882;