5-31446609-T-C

Variant names:

• chr5-31446609-T-C
• rs10067066
• NM_001382508.1:c.2882+1938A>G

Variant summary

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

The NM_001382508.1(DROSHA):​c.2882+1938A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 150,364 control chromosomes in the GnomAD database, including 1,661 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 0.13 (1661 hom., cov: 29)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 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.2882+1938A>G		intron	N/A	NP_001369437.1
	DROSHA	NM_013235.5		c.2882+1938A>G		intron	N/A	NP_037367.3
	DROSHA	NM_001100412.2		c.2771+1938A>G		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.2882+1938A>G		intron	N/A	ENSP00000339845.3
	DROSHA	ENST00000511367.6	TSL:1	c.2882+1938A>G		intron	N/A	ENSP00000425979.2
	DROSHA	ENST00000513349.5	TSL:1	c.2771+1938A>G		intron	N/A	ENSP00000424161.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 18863 AN: 150252 Hom.: 1650 Cov.: 29

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.0712

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.126 AC: 18899 AN: 150364 Hom.: 1661 Cov.: 29 AF XY: 0.123 AC XY: 9053 AN XY: 73380

African (AFR) AF: 0.247 AC: 10053 AN: 40744

American (AMR) AF: 0.0970 AC: 1468 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3462

East Asian (EAS) AF: 0.220 AC: 1124 AN: 5104

South Asian (SAS) AF: 0.0321 AC: 154 AN: 4792

European-Finnish (FIN) AF: 0.0712 AC: 718 AN: 10082

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0700 AC: 4742 AN: 67754

Other (OTH) AF: 0.108 AC: 225 AN: 2084

Alfa AF: 0.0919 Hom.: 1934

Bravo AF: 0.136

Asia WGS AF: 0.135 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.8
DANN	Benign	0.71
PhyloP100		-0.23
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: rs10067066; hg19: chr5-31446716;