ENST00000495826.5:n.3882G>A

Variant names:

• chr22-20111059-G-A
• rs720012
• ENST00000495826.5:n.3882G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000495826.5(DGCR8):​n.3882G>A variant causes a non coding transcript exon 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 ENST00000495826.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 23 publications found

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]

ENSG00000243762 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DGCR8	NM_022720.7	c.*951G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000351989.8	NP_073557.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR8	ENST00000351989.8	c.*951G>A		3_prime_UTR_variant	Exon 14 of 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

African (AFR) AF: 0.0269 AC: 193 AN: 7178

American (AMR) AF: 0.303 AC: 2251 AN: 7432

Ashkenazi Jewish (ASJ) AF: 0.0884 AC: 817 AN: 9240

East Asian (EAS) AF: 0.448 AC: 10253 AN: 22892

South Asian (SAS) AF: 0.263 AC: 584 AN: 2224

European-Finnish (FIN) AF: 0.149 AC: 3095 AN: 20826

Middle Eastern (MID) AF: 0.0681 AC: 88 AN: 1292

European-Non Finnish (NFE) AF: 0.128 AC: 20187 AN: 158002

Other (OTH) AF: 0.152 AC: 2481 AN: 16362

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

African (AFR) AF: 0.0279 AC: 1156 AN: 41502

American (AMR) AF: 0.257 AC: 3928 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0802 AC: 278 AN: 3468

East Asian (EAS) AF: 0.519 AC: 2691 AN: 5180

South Asian (SAS) AF: 0.258 AC: 1245 AN: 4826

European-Finnish (FIN) AF: 0.152 AC: 1606 AN: 10596

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8567 AN: 67988

Other (OTH) AF: 0.133 AC: 280 AN: 2108

Alfa AF: 0.123 Hom.: 1513

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
PhyloP100		1.8
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: rs720012; hg19: chr22-20098582;