5-31408606-T-C

Variant names:

• chr5-31408606-T-C
• rs615435
• NM_001382508.1:c.3854+450A>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.3854+450A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 158,422 control chromosomes in the GnomAD database, including 2,131 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 0.16 (2065 hom., cov: 32)
  • Exomes 𝑓: 0.13 (66 hom.)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	NM_001382508.1	MANE Select	c.3854+450A>G		intron	N/A	NP_001369437.1
	DROSHA	NM_013235.5		c.3854+450A>G		intron	N/A	NP_037367.3
	DROSHA	NM_001100412.2		c.3743+450A>G		intron	N/A	NP_001093882.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	ENST00000344624.8	TSL:5 MANE Select	c.3854+450A>G		intron	N/A	ENSP00000339845.3
	DROSHA	ENST00000511367.6	TSL:1	c.3854+450A>G		intron	N/A	ENSP00000425979.2
	DROSHA	ENST00000513349.5	TSL:1	c.3743+450A>G		intron	N/A	ENSP00000424161.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23857 AN: 151990 Hom.: 2060 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.126 AC: 793 AN: 6314 Hom.: 66 AF XY: 0.129 AC XY: 422 AN XY: 3272

African (AFR) AF: 0.118 AC: 4 AN: 34

American (AMR) AF: 0.149 AC: 217 AN: 1458

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 2 AN: 46

East Asian (EAS) AF: 0.244 AC: 42 AN: 172

South Asian (SAS) AF: 0.148 AC: 104 AN: 704

European-Finnish (FIN) AF: 0.0577 AC: 3 AN: 52

Middle Eastern (MID) AF: 0.100 AC: 1 AN: 10

European-Non Finnish (NFE) AF: 0.109 AC: 386 AN: 3556

Other (OTH) AF: 0.121 AC: 34 AN: 282

GnomAD4 genome AF: 0.157 AC: 23887 AN: 152108 Hom.: 2065 Cov.: 32 AF XY: 0.160 AC XY: 11911 AN XY: 74358

African (AFR) AF: 0.135 AC: 5591 AN: 41490

American (AMR) AF: 0.208 AC: 3171 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1516 AN: 5152

South Asian (SAS) AF: 0.215 AC: 1036 AN: 4812

European-Finnish (FIN) AF: 0.148 AC: 1570 AN: 10588

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.142 AC: 9636 AN: 68010

Other (OTH) AF: 0.167 AC: 352 AN: 2112

Alfa AF: 0.0968 Hom.: 176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.63
PhyloP100		0.38
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: rs615435; hg19: chr5-31408713;