rs16901121

Variant names:

• chr5-31418108-C-T
• rs16901121
• NM_001382508.1:c.3525+3164G>A

Variant summary

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

The NM_001382508.1(DROSHA):​c.3525+3164G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,080 control chromosomes in the GnomAD database, including 4,303 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 0.22 (4303 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 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.3525+3164G>A		intron	N/A	NP_001369437.1
	DROSHA	NM_013235.5		c.3525+3164G>A		intron	N/A	NP_037367.3
	DROSHA	NM_001100412.2		c.3414+3164G>A		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.3525+3164G>A		intron	N/A	ENSP00000339845.3
	DROSHA	ENST00000511367.6	TSL:1	c.3525+3164G>A		intron	N/A	ENSP00000425979.2
	DROSHA	ENST00000513349.5	TSL:1	c.3414+3164G>A		intron	N/A	ENSP00000424161.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33947 AN: 151962 Hom.: 4286 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.224 AC: 34009 AN: 152080 Hom.: 4303 Cov.: 32 AF XY: 0.224 AC XY: 16651 AN XY: 74330

African (AFR) AF: 0.337 AC: 13976 AN: 41458

American (AMR) AF: 0.237 AC: 3621 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3468

East Asian (EAS) AF: 0.289 AC: 1493 AN: 5168

South Asian (SAS) AF: 0.214 AC: 1029 AN: 4814

European-Finnish (FIN) AF: 0.157 AC: 1660 AN: 10592

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.158 AC: 10731 AN: 67980

Other (OTH) AF: 0.216 AC: 457 AN: 2114

Alfa AF: 0.207 Hom.: 736

Bravo AF: 0.233

Asia WGS AF: 0.321 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.7
DANN	Benign	0.61
PhyloP100		2.3
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: rs16901121; hg19: chr5-31418215;