rs720012

Positions:

• chr22-20111059-G-A
• chr22-20111059-G-C
• chr22-20111059-G-T

Variant summary

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

The NM_022720.7(DGCR8):​c.*951G>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 0.15 in 397,614 control chromosomes in the GnomAD database, including 6,934 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 0.13 (2230 hom., cov: 33)
  • Exomes 𝑓: 0.16 (4704 hom.)
• Consequence: DGCR8 NM_022720.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80

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]

DGCR8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGCR8	NM_022720.7	c.*951G>A		3_prime_UTR_variant	14/14	ENST00000351989.8	NP_073557.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGCR8	ENST00000351989.8	c.*951G>A		3_prime_UTR_variant	14/14	1	NM_022720.7	ENSP00000263209.3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19816 AN: 152048 Hom.: 2224 Cov.: 33

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.0802

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.163 AC: 39949 AN: 245448 Hom.: 4704 Cov.: 0 AF XY: 0.161 AC XY: 20031 AN XY: 124388

Gnomad4 AFR exome AF: 0.0269

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.0884

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.130 AC: 19830 AN: 152166 Hom.: 2230 Cov.: 33 AF XY: 0.139 AC XY: 10359 AN XY: 74366

Gnomad4 AFR AF: 0.0279

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.0802

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.133

Alfa AF: 0.121 Hom.: 1092

Bravo AF: 0.134

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.9
DANN	Benign	0.52

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: rs720012; hg19: chr22-20098582;