rs10078886

Variant names:

• chr5-31427334-T-A
• rs10078886
• NM_001382508.1:c.3216+2141A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-31427334-T-A
• chr5-31427334-T-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.3216+2141A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 151,944 control chromosomes in the GnomAD database, including 3,871 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 0.21 (3871 hom., cov: 31)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 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.3216+2141A>T		intron	N/A	NP_001369437.1
	DROSHA	NM_013235.5		c.3216+2141A>T		intron	N/A	NP_037367.3
	DROSHA	NM_001100412.2		c.3105+2141A>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.3216+2141A>T		intron	N/A	ENSP00000339845.3
	DROSHA	ENST00000511367.6	TSL:1	c.3216+2141A>T		intron	N/A	ENSP00000425979.2
	DROSHA	ENST00000513349.5	TSL:1	c.3105+2141A>T		intron	N/A	ENSP00000424161.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32589 AN: 151826 Hom.: 3854 Cov.: 31

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.215 AC: 32643 AN: 151944 Hom.: 3871 Cov.: 31 AF XY: 0.216 AC XY: 16019 AN XY: 74246

African (AFR) AF: 0.304 AC: 12583 AN: 41398

American (AMR) AF: 0.234 AC: 3580 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 765 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1538 AN: 5160

South Asian (SAS) AF: 0.215 AC: 1036 AN: 4814

European-Finnish (FIN) AF: 0.157 AC: 1658 AN: 10554

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10736 AN: 67950

Other (OTH) AF: 0.211 AC: 446 AN: 2112

Alfa AF: 0.163 Hom.: 282

Bravo AF: 0.223

Asia WGS AF: 0.337 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.66
DANN	Benign	0.61
PhyloP100		-0.98
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: rs10078886; hg19: chr5-31427441;