rs17409275

chr5-31514020-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382508.1(DROSHA):c.1290+968G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,738 control chromosomes in the GnomAD database, including 10,152 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 0.34 (10152 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DROSHA	NM_001382508.1	c.1290+968G>A		intron_variant		ENST00000344624.8
DROSHA	NM_001100412.2	c.1179+968G>A		intron_variant
DROSHA	NM_013235.5	c.1290+968G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DROSHA	ENST00000344624.8	c.1290+968G>A		intron_variant		5	NM_001382508.1	P4
DROSHA	ENST00000511367.6	c.1290+968G>A		intron_variant		1		P4
DROSHA	ENST00000512076.1	c.574+968G>A		intron_variant		1
DROSHA	ENST00000513349.5	c.1179+968G>A		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51439 AN: 151620 Hom.: 10156 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.0396

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.339 AC: 51433 AN: 151738 Hom.: 10152 Cov.: 32 AF XY: 0.337 AC XY: 24982 AN XY: 74122

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.0395

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.352

Alfa AF: 0.425 Hom.: 7862

Bravo AF: 0.324

Asia WGS AF: 0.212 AC: 740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.81
Dann	Benign	0.42

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

Other links and lift over

dbSNP: rs17409275; hg19: chr5-31514127;