rs10520985

Variant names:

• chr5-31524458-G-A
• rs10520985
• NM_001382508.1:c.854+1621C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-31524458-G-A
• chr5-31524458-G-C

Variant summary

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

The NM_001382508.1(DROSHA):​c.854+1621C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,050 control chromosomes in the GnomAD database, including 12,822 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 0.39 (12822 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.854+1621C>T		intron_variant	Intron 5 of 35	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5	c.854+1621C>T		intron_variant	Intron 4 of 34		NP_037367.3
DROSHA	NM_001100412.2	c.854+1621C>T		intron_variant	Intron 5 of 34		NP_001093882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.854+1621C>T		intron_variant	Intron 5 of 35	5	NM_001382508.1	ENSP00000339845.3

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58811 AN: 151932 Hom.: 12822 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.387 AC: 58827 AN: 152050 Hom.: 12822 Cov.: 32 AF XY: 0.388 AC XY: 28814 AN XY: 74300

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.397

Alfa AF: 0.319 Hom.: 1156

Bravo AF: 0.372

Asia WGS AF: 0.308 AC: 1077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.81

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: rs10520985; hg19: chr5-31524565;