Variant 5-31401340-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001382508.1(DROSHA):c.*92T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 1,532,660 control chromosomes in the GnomAD database, including 436,300 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 0.64 ( 33986 hom., cov: 32)

Exomes 𝑓: 0.75 ( 402314 hom. )

Consequence

DROSHA
NM_001382508.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.46

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:

DROSHA (HGNC:):

DROSHA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
DROSHA	NM_001382508.1 linkuse as main transcript	c.*92T>C	3_prime_UTR_variant	36/36	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5 linkuse as main transcript	c.*92T>C	3_prime_UTR_variant	35/35		NP_037367.3	Q9NRR4-1
DROSHA	NM_001100412.2 linkuse as main transcript	c.*92T>C	3_prime_UTR_variant	35/35		NP_001093882.1	Q9NRR4-4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DROSHA	ENST00000344624 linkuse as main transcript	c.*92T>C	3_prime_UTR_variant	36/36	5	NM_001382508.1	ENSP00000339845.3	Q9NRR4-1
DROSHA	ENST00000511367 linkuse as main transcript	c.*92T>C	3_prime_UTR_variant	35/35	1		ENSP00000425979.2	Q9NRR4-1
DROSHA	ENST00000513349 linkuse as main transcript	c.*92T>C	3_prime_UTR_variant	35/35	1		ENSP00000424161.1	Q9NRR4-4
DROSHA	ENST00000514927.6 linkuse as main transcript	n.374T>C	non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.643

AC:

97755

AN:

151964

Hom.:

33984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.713

Gnomad AMR

AF:

0.669

Gnomad ASJ

AF:

0.676

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.617

Gnomad FIN

AF:

0.726

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.800

Gnomad OTH

AF:

0.663

GnomAD3 exomes

AF:

0.687

AC:

170158

AN:

247826

Hom.:

61290

AF XY:

0.693

AC XY:

93192

AN XY:

134526

show subpopulations

Gnomad AFR exome

AF:

0.378

Gnomad AMR exome

AF:

0.654

Gnomad ASJ exome

AF:

0.687

Gnomad EAS exome

AF:

0.326

Gnomad SAS exome

AF:

0.628

Gnomad FIN exome

AF:

0.745

Gnomad NFE exome

AF:

0.799

Gnomad OTH exome

AF:

0.729

GnomAD4 exome

AF:

0.754

AC:

1041601

AN:

1380578

Hom.:

402314

Cov.:

AF XY:

0.752

AC XY:

519573

AN XY:

690962

show subpopulations

Gnomad4 AFR exome

AF:

0.372

Gnomad4 AMR exome

AF:

0.656

Gnomad4 ASJ exome

AF:

0.695

Gnomad4 EAS exome

AF:

0.277

Gnomad4 SAS exome

AF:

0.627

Gnomad4 FIN exome

AF:

0.748

Gnomad4 NFE exome

AF:

0.801

Gnomad4 OTH exome

AF:

0.712

GnomAD4 genome

AF:

0.643

AC:

97779

AN:

152082

Hom.:

33986

Cov.:

AF XY:

0.638

AC XY:

47403

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.394

Gnomad4 AMR

AF:

0.669

Gnomad4 ASJ

AF:

0.676

Gnomad4 EAS

AF:

0.318

Gnomad4 SAS

AF:

0.618

Gnomad4 FIN

AF:

0.726

Gnomad4 NFE

AF:

0.800

Gnomad4 OTH

AF:

0.658

Alfa

AF:

0.761

Hom.:

69622

Bravo

AF:

0.626

Asia WGS

AF:

0.456

AC:

1590

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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