dbSNP rs1640299: DGCR8:n.3659T>G (chr22-20110836-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.206

Publications

38 publications found

Variant links:

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 links:

ENSG00000243762 (HGNC:):

ENSG00000243762 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.*728T>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000351989.8	NP_073557.3	Q8WYQ5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR8	ENST00000351989.8 link	c.*728T>G		3_prime_UTR_variant	Exon 14 of 14	1	NM_022720.7	ENSP00000263209.3		Q8WYQ5-1

Frequencies

GnomAD3 genomes

AF:

0.436

AC:

66151

AN:

151842

Hom.:

14909

Cov.:

show subpopulations

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.:

AF XY:

0.454

AC XY:

10549

AN XY:

23248

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

548

1095

1643

2190

2738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.435

AC:

66176

AN:

151960

Hom.:

14911

Cov.:

AF XY:

0.434

AC XY:

32210

AN XY:

74262

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1846

3692

5539

7385

9231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.55

PhyloP100

0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over