chr22-20110836-T-G

Variant names:

• chr22-20110836-T-G
• rs1640299
• ENST00000495826.5:n.3659T>G

Variant summary

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

The ENST00000495826.5(DGCR8):​n.3659T>G 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 0.44 in 198,022 control chromosomes in the GnomAD database, including 20,004 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 0.44 (14911 hom., cov: 32)
  • Exomes 𝑓: 0.46 (5093 hom.)
• Consequence: DGCR8 ENST00000495826.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 38 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGCR8	NM_022720.7	c.*728T>G		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.*728T>G		3_prime_UTR_variant	Exon 14 of 14	1	NM_022720.7	ENSP00000263209.3

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66151 AN: 151842 Hom.: 14909 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.475

GnomAD4 exome AF: 0.455 AC: 20977 AN: 46062 Hom.: 5093 Cov.: 0 AF XY: 0.454 AC XY: 10549 AN XY: 23248

African (AFR) AF: 0.341 AC: 629 AN: 1846

American (AMR) AF: 0.422 AC: 511 AN: 1212

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 1303 AN: 2104

East Asian (EAS) AF: 0.295 AC: 1138 AN: 3864

South Asian (SAS) AF: 0.374 AC: 157 AN: 420

European-Finnish (FIN) AF: 0.425 AC: 977 AN: 2300

Middle Eastern (MID) AF: 0.459 AC: 113 AN: 246

European-Non Finnish (NFE) AF: 0.474 AC: 14673 AN: 30924

Other (OTH) AF: 0.469 AC: 1476 AN: 3146

GnomAD4 genome AF: 0.435 AC: 66176 AN: 151960 Hom.: 14911 Cov.: 32 AF XY: 0.434 AC XY: 32210 AN XY: 74262

African (AFR) AF: 0.367 AC: 15213 AN: 41406

American (AMR) AF: 0.445 AC: 6795 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2155 AN: 3466

East Asian (EAS) AF: 0.249 AC: 1287 AN: 5164

South Asian (SAS) AF: 0.416 AC: 2001 AN: 4806

European-Finnish (FIN) AF: 0.442 AC: 4669 AN: 10566

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32465 AN: 67954

Other (OTH) AF: 0.471 AC: 993 AN: 2110

Alfa AF: 0.476 Hom.: 29944

Bravo AF: 0.435

Asia WGS AF: 0.328 AC: 1142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.4
DANN	Benign	0.55
PhyloP100		0.21
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: rs1640299; hg19: chr22-20098359;