NM_001382508.1:c.3217-1210C>A

Variant names:

• chr5-31425681-G-T
• rs615344
• NM_001382508.1:c.3217-1210C>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.3217-1210C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,804 control chromosomes in the GnomAD database, including 11,599 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 0.35 (11599 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 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.3217-1210C>A		intron	N/A	NP_001369437.1
	DROSHA	NM_013235.5		c.3217-1210C>A		intron	N/A	NP_037367.3
	DROSHA	NM_001100412.2		c.3106-1210C>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.3217-1210C>A		intron	N/A	ENSP00000339845.3
	DROSHA	ENST00000511367.6	TSL:1	c.3217-1210C>A		intron	N/A	ENSP00000425979.2
	DROSHA	ENST00000513349.5	TSL:1	c.3106-1210C>A		intron	N/A	ENSP00000424161.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53202 AN: 151686 Hom.: 11566 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.351 AC: 53287 AN: 151804 Hom.: 11599 Cov.: 32 AF XY: 0.354 AC XY: 26235 AN XY: 74168

African (AFR) AF: 0.603 AC: 24938 AN: 41376

American (AMR) AF: 0.293 AC: 4471 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1084 AN: 3470

East Asian (EAS) AF: 0.567 AC: 2911 AN: 5134

South Asian (SAS) AF: 0.368 AC: 1764 AN: 4794

European-Finnish (FIN) AF: 0.261 AC: 2746 AN: 10530

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.211 AC: 14331 AN: 67946

Other (OTH) AF: 0.326 AC: 685 AN: 2100

Alfa AF: 0.241 Hom.: 8520

Bravo AF: 0.365

Asia WGS AF: 0.489 AC: 1699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.35
PhyloP100		-0.22
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: rs615344; hg19: chr5-31425788;