5-31416141-A-G

Variant names:

• chr5-31416141-A-G
• rs3792830
• NM_001382508.1:c.3525+5131T>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.3525+5131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0941 in 152,250 control chromosomes in the GnomAD database, including 905 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 0.094 (905 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 9 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=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 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+5131T>C		intron	N/A	NP_001369437.1
	DROSHA	NM_013235.5		c.3525+5131T>C		intron	N/A	NP_037367.3
	DROSHA	NM_001100412.2		c.3414+5131T>C		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+5131T>C		intron	N/A	ENSP00000339845.3
	DROSHA	ENST00000511367.6	TSL:1	c.3525+5131T>C		intron	N/A	ENSP00000425979.2
	DROSHA	ENST00000513349.5	TSL:1	c.3414+5131T>C		intron	N/A	ENSP00000424161.1

Frequencies

GnomAD3 genomes AF: 0.0941 AC: 14313 AN: 152132 Hom.: 899 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0875

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

GnomAD4 genome AF: 0.0941 AC: 14324 AN: 152250 Hom.: 905 Cov.: 32 AF XY: 0.0947 AC XY: 7047 AN XY: 74444

African (AFR) AF: 0.171 AC: 7102 AN: 41528

American (AMR) AF: 0.0851 AC: 1302 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 341 AN: 3468

East Asian (EAS) AF: 0.167 AC: 866 AN: 5180

South Asian (SAS) AF: 0.107 AC: 517 AN: 4824

European-Finnish (FIN) AF: 0.0524 AC: 556 AN: 10610

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0500 AC: 3400 AN: 68016

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.0655 Hom.: 1827

Bravo AF: 0.102

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		0.028
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: rs3792830; hg19: chr5-31416248;