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. The variant received -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
• 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=-0.78).
• 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

African (AFR) AF: 0.183 AC: 7569 AN: 41468

American (AMR) AF: 0.418 AC: 6389 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1383 AN: 3472

East Asian (EAS) AF: 0.198 AC: 1023 AN: 5176

South Asian (SAS) AF: 0.479 AC: 2310 AN: 4824

European-Finnish (FIN) AF: 0.466 AC: 4909 AN: 10534

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33833 AN: 67974

Other (OTH) AF: 0.397 AC: 836 AN: 2106

Alfa AF: 0.386 Hom.: 3641

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
PhyloP100		1.2
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: rs10520985; hg19: chr5-31524565;