rs10461898

Variant names:

• chr5-31520127-G-A
• rs10461898
• NM_001382508.1:c.947+996C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-31520127-G-A
• chr5-31520127-G-T

Variant summary

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

The NM_001382508.1(DROSHA):​c.947+996C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,702 control chromosomes in the GnomAD database, including 10,949 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 0.37 (10949 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 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.947+996C>T		intron	N/A	NP_001369437.1
	DROSHA	NM_013235.5		c.947+996C>T		intron	N/A	NP_037367.3
	DROSHA	NM_001100412.2		c.947+996C>T		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.947+996C>T		intron	N/A	ENSP00000339845.3
	DROSHA	ENST00000511367.6	TSL:1	c.947+996C>T		intron	N/A	ENSP00000425979.2
	DROSHA	ENST00000513349.5	TSL:1	c.947+996C>T		intron	N/A	ENSP00000424161.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56212 AN: 151582 Hom.: 10934 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.371 AC: 56275 AN: 151702 Hom.: 10949 Cov.: 32 AF XY: 0.375 AC XY: 27768 AN XY: 74142

African (AFR) AF: 0.393 AC: 16269 AN: 41376

American (AMR) AF: 0.382 AC: 5829 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1416 AN: 3472

East Asian (EAS) AF: 0.780 AC: 4015 AN: 5148

South Asian (SAS) AF: 0.347 AC: 1667 AN: 4810

European-Finnish (FIN) AF: 0.402 AC: 4215 AN: 10478

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

European-Non Finnish (NFE) AF: 0.320 AC: 21690 AN: 67854

Other (OTH) AF: 0.355 AC: 750 AN: 2112

Alfa AF: 0.241 Hom.: 693

Bravo AF: 0.373

Asia WGS AF: 0.563 AC: 1954 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.41
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: rs10461898; hg19: chr5-31520234;