22-20111359-T-C

Variant names:

• chr22-20111359-T-C
• rs720014
• ENST00000495826.5:n.4182T>C

Variant summary

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

The ENST00000495826.5(DGCR8):​n.4182T>C 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 0.232 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 ENST00000495826.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 12 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000495826.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR8	NM_022720.7	MANE Select	c.*1251T>C		3_prime_UTR	Exon 14 of 14	NP_073557.3
	DGCR8	NM_001190326.2		c.*1251T>C		3_prime_UTR	Exon 13 of 13	NP_001177255.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR8	ENST00000495826.5	TSL:1	n.4182T>C		non_coding_transcript_exon	Exon 12 of 12
	DGCR8	ENST00000498171.5	TSL:1	n.3143T>C		non_coding_transcript_exon	Exon 11 of 11
	DGCR8	ENST00000351989.8	TSL:1 MANE Select	c.*1251T>C		3_prime_UTR	Exon 14 of 14	ENSP00000263209.3

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

African (AFR) AF: 0.127 AC: 911 AN: 7182

American (AMR) AF: 0.275 AC: 2045 AN: 7432

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 2757 AN: 9242

East Asian (EAS) AF: 0.252 AC: 5763 AN: 22890

South Asian (SAS) AF: 0.125 AC: 380 AN: 3036

European-Finnish (FIN) AF: 0.230 AC: 4789 AN: 20832

Middle Eastern (MID) AF: 0.285 AC: 369 AN: 1294

European-Non Finnish (NFE) AF: 0.239 AC: 37847 AN: 158108

Other (OTH) AF: 0.234 AC: 3837 AN: 16378

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

African (AFR) AF: 0.138 AC: 5553 AN: 40320

American (AMR) AF: 0.293 AC: 3892 AN: 13262

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1048 AN: 3288

East Asian (EAS) AF: 0.216 AC: 951 AN: 4398

South Asian (SAS) AF: 0.170 AC: 698 AN: 4102

European-Finnish (FIN) AF: 0.264 AC: 2411 AN: 9136

Middle Eastern (MID) AF: 0.326 AC: 88 AN: 270

European-Non Finnish (NFE) AF: 0.248 AC: 15923 AN: 64122

Other (OTH) AF: 0.241 AC: 464 AN: 1926

Alfa AF: 0.229 Hom.: 3093

Bravo AF: 0.209

Asia WGS AF: 0.148 AC: 506 AN: 3416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.67
PhyloP100		-0.26
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: rs720014; hg19: chr22-20098882;