rs682902

Variant names:

• chr5-31423587-T-C
• rs682902
• NM_001382508.1:c.3262-643A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382508.1(DROSHA):​c.3262-643A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,028 control chromosomes in the GnomAD database, including 12,361 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 0.36 (12361 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382508.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	NM_001382508.1	MANE Select	c.3262-643A>G		intron	N/A	NP_001369437.1
	DROSHA	NM_013235.5		c.3262-643A>G		intron	N/A	NP_037367.3
	DROSHA	NM_001100412.2		c.3151-643A>G		intron	N/A	NP_001093882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	ENST00000344624.8	TSL:5 MANE Select	c.3262-643A>G		intron	N/A	ENSP00000339845.3
	DROSHA	ENST00000511367.6	TSL:1	c.3262-643A>G		intron	N/A	ENSP00000425979.2
	DROSHA	ENST00000513349.5	TSL:1	c.3151-643A>G		intron	N/A	ENSP00000424161.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54867 AN: 151908 Hom.: 12324 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.338

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.361 AC: 54957 AN: 152028 Hom.: 12361 Cov.: 32 AF XY: 0.365 AC XY: 27152 AN XY: 74316

African (AFR) AF: 0.608 AC: 25192 AN: 41428

American (AMR) AF: 0.338 AC: 5155 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1090 AN: 3470

East Asian (EAS) AF: 0.670 AC: 3462 AN: 5168

South Asian (SAS) AF: 0.377 AC: 1818 AN: 4824

European-Finnish (FIN) AF: 0.260 AC: 2750 AN: 10578

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.212 AC: 14404 AN: 67984

Other (OTH) AF: 0.343 AC: 725 AN: 2112

Alfa AF: 0.257 Hom.: 3101

Bravo AF: 0.379

Asia WGS AF: 0.540 AC: 1873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.76
PhyloP100		-0.018
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs682902; hg19: chr5-31423694;