rs16901096

Variant names:

• chr5-31407749-C-T
• rs16901096
• NM_001382508.1:c.3855-804G>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.3855-804G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 152,210 control chromosomes in the GnomAD database, including 133 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 0.015 (133 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 2 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 = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.3855-804G>A		intron_variant	Intron 33 of 35	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5	c.3855-804G>A		intron_variant	Intron 32 of 34		NP_037367.3
DROSHA	NM_001100412.2	c.3744-804G>A		intron_variant	Intron 32 of 34		NP_001093882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.3855-804G>A		intron_variant	Intron 33 of 35	5	NM_001382508.1	ENSP00000339845.3
DROSHA	ENST00000511367.6	c.3855-804G>A		intron_variant	Intron 32 of 34	1		ENSP00000425979.2
DROSHA	ENST00000513349.5	c.3744-804G>A		intron_variant	Intron 32 of 34	1		ENSP00000424161.1
DROSHA	ENST00000511778.5	n.971-804G>A		intron_variant	Intron 5 of 7	3

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2270 AN: 152090 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.000990

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.0562

Gnomad FIN AF: 0.0507

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00351

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.0149 AC: 2273 AN: 152210 Hom.: 133 Cov.: 32 AF XY: 0.0192 AC XY: 1429 AN XY: 74420

African (AFR) AF: 0.000987 AC: 41 AN: 41546

American (AMR) AF: 0.00334 AC: 51 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3468

East Asian (EAS) AF: 0.208 AC: 1076 AN: 5176

South Asian (SAS) AF: 0.0562 AC: 271 AN: 4818

European-Finnish (FIN) AF: 0.0507 AC: 537 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00352 AC: 239 AN: 67994

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.0106 Hom.: 8

Bravo AF: 0.0115

Asia WGS AF: 0.107 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.72
PhyloP100		0.0010
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: rs16901096; hg19: chr5-31407856;