Variant 5-31510999-G-T 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.1432+36C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,602,116 control chromosomes in the GnomAD database, including 55,653 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 0.23 ( 4340 hom., cov: 32)

Exomes 𝑓: 0.26 ( 51313 hom. )

Consequence

DROSHA
NM_001382508.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.413

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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
DROSHA	NM_001382508.1 linkuse as main transcript	c.1432+36C>A	intron_variant	ENST00000344624.8	NP_001369437.1
DROSHA	NM_001100412.2 linkuse as main transcript	c.1321+36C>A	intron_variant		NP_001093882.1
DROSHA	NM_013235.5 linkuse as main transcript	c.1432+36C>A	intron_variant		NP_037367.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8 linkuse as main transcript	c.1432+36C>A	intron_variant	5	NM_001382508.1	ENSP00000339845	P4	Q9NRR4-1
DROSHA	ENST00000511367.6 linkuse as main transcript	c.1432+36C>A	intron_variant	1		ENSP00000425979	P4	Q9NRR4-1
DROSHA	ENST00000512076.1 linkuse as main transcript	c.716+36C>A	intron_variant	1		ENSP00000422745
DROSHA	ENST00000513349.5 linkuse as main transcript	c.1321+36C>A	intron_variant	1		ENSP00000424161	A1	Q9NRR4-4

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34702

AN:

151948

Hom.:

4342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.230

GnomAD3 exomes

AF:

0.267

AC:

64016

AN:

240162

Hom.:

8914

AF XY:

0.270

AC XY:

35225

AN XY:

130256

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.262

Gnomad ASJ exome

AF:

0.304

Gnomad EAS exome

AF:

0.368

Gnomad SAS exome

AF:

0.300

Gnomad FIN exome

AF:

0.256

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.263

AC:

380812

AN:

1450050

Hom.:

51313

Cov.:

AF XY:

0.264

AC XY:

190496

AN XY:

720234

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.261

Gnomad4 ASJ exome

AF:

0.298

Gnomad4 EAS exome

AF:

0.392

Gnomad4 SAS exome

AF:

0.301

Gnomad4 FIN exome

AF:

0.259

Gnomad4 NFE exome

AF:

0.259

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.228

AC:

34719

AN:

152066

Hom.:

4340

Cov.:

AF XY:

0.229

AC XY:

17051

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.255

Gnomad4 ASJ

AF:

0.307

Gnomad4 EAS

AF:

0.365

Gnomad4 SAS

AF:

0.296

Gnomad4 FIN

AF:

0.263

Gnomad4 NFE

AF:

0.258

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.254

Hom.:

8973

Bravo

AF:

0.221

Asia WGS

AF:

0.335

AC:

1162

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.98

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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