dbSNP rs11089328: DGCR8:c.1606+110A>G (chr22-20092080-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_022720.7(DGCR8):c.1606+110A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 836,726 control chromosomes in the GnomAD database, including 79,356 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 0.41 ( 13294 hom., cov: 32)

Exomes 𝑓: 0.43 ( 66062 hom. )

Consequence

DGCR8
NM_022720.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.973

Publications

14 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:

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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGCR8	NM_022720.7 link	c.1606+110A>G		intron_variant	Intron 7 of 13	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.1606+110A>G		intron_variant	Intron 7 of 13	1	NM_022720.7	ENSP00000263209.3		Q8WYQ5-1

Frequencies

GnomAD3 genomes

AF:

0.410

AC:

62282

AN:

151930

Hom.:

13282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.497

Gnomad ASJ

AF:

0.415

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.550

Gnomad FIN

AF:

0.453

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.426

GnomAD4 exome

AF:

0.430

AC:

294104

AN:

684678

Hom.:

66062

AF XY:

0.434

AC XY:

154126

AN XY:

354954

show subpopulations

African (AFR)

AF:

0.316

AC:

5491

AN:

17372

American (AMR)

AF:

0.567

AC:

15829

AN:

27912

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

7314

AN:

17714

East Asian (EAS)

AF:

0.634

AC:

20343

AN:

32110

South Asian (SAS)

AF:

0.551

AC:

32328

AN:

58624

European-Finnish (FIN)

AF:

0.445

AC:

18736

AN:

42106

Middle Eastern (MID)

AF:

0.313

AC:

1286

AN:

4110

European-Non Finnish (NFE)

AF:

0.395

AC:

178206

AN:

450866

Other (OTH)

AF:

0.430

AC:

14571

AN:

33864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

8113

16225

24338

32450

40563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3356

6712

10068

13424

16780

<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:

0.410

AC:

62335

AN:

152048

Hom.:

13294

Cov.:

AF XY:

0.420

AC XY:

31177

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.336

AC:

13945

AN:

41460

American (AMR)

AF:

0.498

AC:

7617

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.415

AC:

1440

AN:

3468

East Asian (EAS)

AF:

0.673

AC:

3474

AN:

5162

South Asian (SAS)

AF:

0.548

AC:

2640

AN:

4814

European-Finnish (FIN)

AF:

0.453

AC:

4782

AN:

10554

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.398

AC:

27073

AN:

67978

Other (OTH)

AF:

0.427

AC:

901

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1872

3743

5615

7486

9358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<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:

0.407

Hom.:

21657

Bravo

AF:

0.411

Asia WGS

AF:

0.561

AC:

1948

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

(source)

DANN

Benign

0.17

PhyloP100

-0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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