Genetic Variant ENST00000495826.5:n.4631G>A (chr22-20111808-G-A) – 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.4631G>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 0.212 in 204,996 control chromosomes in the GnomAD database, including 5,275 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 0.21 ( 3545 hom., cov: 31)

Exomes 𝑓: 0.22 ( 1730 hom. )

Consequence

DGCR8
ENST00000495826.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.262

Publications

41 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:

TRMT2A (HGNC:24974): (tRNA methyltransferase 2 homolog A) The protein encoded by this gene is of unknown function. However, it is orthologous to the mouse Trmt2a gene and contains an RNA methyltransferase domain. Expression of this gene varies during the cell cycle, with aberrant expression being a possible biomarker in certain breast cancers. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

TRMT2A 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=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGCR8	NM_022720.7 link	c.*1700G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000351989.8	NP_073557.3	Q8WYQ5-1
TRMT2A	NM_022727.6 link	c.*755C>T		downstream_gene_variant		ENST00000252136.12	NP_073564.3	Q8IZ69-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR8	ENST00000351989.8 link	c.*1700G>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_022720.7	ENSP00000263209.3		Q8WYQ5-1
TRMT2A	ENST00000252136.12 link	c.*755C>T		downstream_gene_variant		1	NM_022727.6	ENSP00000252136.7		Q8IZ69-1

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31333

AN:

150656

Hom.:

3545

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.233

Gnomad OTH

AF:

0.222

GnomAD4 exome

AF:

0.223

AC:

12070

AN:

54224

Hom.:

1730

Cov.:

AF XY:

0.224

AC XY:

6070

AN XY:

27090

show subpopulations

African (AFR)

AF:

0.107

AC:

245

AN:

2280

American (AMR)

AF:

0.256

AC:

390

AN:

1526

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

647

AN:

1996

East Asian (EAS)

AF:

0.219

AC:

1159

AN:

5298

South Asian (SAS)

AF:

0.101

AC:

AN:

514

European-Finnish (FIN)

AF:

0.204

AC:

727

AN:

3570

Middle Eastern (MID)

AF:

0.333

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.226

AC:

7929

AN:

35096

Other (OTH)

AF:

0.227

AC:

835

AN:

3686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

411

822

1233

1644

2055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.208

AC:

31341

AN:

150772

Hom.:

3545

Cov.:

AF XY:

0.209

AC XY:

15374

AN XY:

73606

show subpopulations

African (AFR)

AF:

0.137

AC:

5645

AN:

41086

American (AMR)

AF:

0.257

AC:

3870

AN:

15082

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

1039

AN:

3468

East Asian (EAS)

AF:

0.188

AC:

946

AN:

5044

South Asian (SAS)

AF:

0.144

AC:

683

AN:

4742

European-Finnish (FIN)

AF:

0.249

AC:

2569

AN:

10310

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.233

AC:

15812

AN:

67750

Other (OTH)

AF:

0.218

AC:

457

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1251

2501

3752

5002

6253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<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:

0.229

Hom.:

4627

Bravo

AF:

0.208

Asia WGS

AF:

0.156

AC:

543

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.3

(source)

DANN

Benign

0.78

PhyloP100

0.26

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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