Variant 5-31409008-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001382508.1(DROSHA):c.3854+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,559,842 control chromosomes in the GnomAD database, including 63,483 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 0.35 ( 11711 hom., cov: 32)

Exomes 𝑓: 0.25 ( 51772 hom. )

Consequence

DROSHA
NM_001382508.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0580

Variant links:

Genes affected

DROSHA (HGNC:17904): (drosha ribonuclease III) This gene encodes a ribonuclease (RNase) III double-stranded RNA-specific ribonuclease and subunit of the microprocessor protein complex, which catalyzes the initial processing step of microRNA (miRNA) synthesis. The encoded protein cleaves the stem loop structure from the primary microRNA (pri-miRNA) in the nucleus, yielding the precursor miRNA (pre-miRNA), which is then exported to the cytoplasm for further processing. In a human cell line lacking a functional copy of this gene, canonical miRNA synthesis is reduced. Somatic mutations in this gene have been observed in human patients with kidney cancer. [provided by RefSeq, Sep 2016]

DROSHA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
DROSHA	NM_001382508.1 linkuse as main transcript	c.3854+48A>G	intron_variant	ENST00000344624.8	NP_001369437.1
DROSHA	NM_001100412.2 linkuse as main transcript	c.3743+48A>G	intron_variant		NP_001093882.1
DROSHA	NM_013235.5 linkuse as main transcript	c.3854+48A>G	intron_variant		NP_037367.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8 linkuse as main transcript	c.3854+48A>G		intron_variant		5	NM_001382508.1	ENSP00000339845	P4	Q9NRR4-1

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53293

AN:

151860

Hom.:

11678

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.669

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.318

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.330

GnomAD3 exomes

AF:

0.312

AC:

70573

AN:

226424

Hom.:

13428

AF XY:

0.305

AC XY:

37257

AN XY:

122262

show subpopulations

Gnomad AFR exome

AF:

0.603

Gnomad AMR exome

AF:

0.344

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.664

Gnomad SAS exome

AF:

0.370

Gnomad FIN exome

AF:

0.255

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.273

GnomAD4 exome

AF:

0.246

AC:

345634

AN:

1407864

Hom.:

51772

Cov.:

AF XY:

0.248

AC XY:

173632

AN XY:

701080

show subpopulations

Gnomad4 AFR exome

AF:

0.612

Gnomad4 AMR exome

AF:

0.341

Gnomad4 ASJ exome

AF:

0.298

Gnomad4 EAS exome

AF:

0.711

Gnomad4 SAS exome

AF:

0.370

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.286

GnomAD4 genome

AF:

0.351

AC:

53378

AN:

151978

Hom.:

11711

Cov.:

AF XY:

0.356

AC XY:

26480

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.589

Gnomad4 AMR

AF:

0.328

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.670

Gnomad4 SAS

AF:

0.380

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.201

Gnomad4 OTH

AF:

0.335

Alfa

AF:

0.264

Hom.:

1750

Bravo

AF:

0.368

Asia WGS

AF:

0.539

AC:

1872

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.5

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over