5-31451342-G-A

Variant names:

• chr5-31451342-G-A
• rs6886834
• NM_001382508.1:c.2682+191C>T

Variant summary

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

The NM_001382508.1(DROSHA):​c.2682+191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,154 control chromosomes in the GnomAD database, including 1,846 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 0.14 (1846 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.199 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.2682+191C>T		intron	N/A	NP_001369437.1
	DROSHA	NM_013235.5		c.2682+191C>T		intron	N/A	NP_037367.3
	DROSHA	NM_001100412.2		c.2571+191C>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.2682+191C>T		intron	N/A	ENSP00000339845.3
	DROSHA	ENST00000511367.6	TSL:1	c.2682+191C>T		intron	N/A	ENSP00000425979.2
	DROSHA	ENST00000513349.5	TSL:1	c.2571+191C>T		intron	N/A	ENSP00000424161.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20653 AN: 152036 Hom.: 1848 Cov.: 32

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.136 AC: 20641 AN: 152154 Hom.: 1846 Cov.: 32 AF XY: 0.135 AC XY: 10050 AN XY: 74368

African (AFR) AF: 0.0324 AC: 1347 AN: 41518

American (AMR) AF: 0.205 AC: 3140 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 719 AN: 3472

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5184

South Asian (SAS) AF: 0.136 AC: 656 AN: 4820

European-Finnish (FIN) AF: 0.158 AC: 1671 AN: 10570

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12394 AN: 67992

Other (OTH) AF: 0.151 AC: 319 AN: 2110

Alfa AF: 0.164 Hom.: 1651

Bravo AF: 0.137

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.016
DANN	Benign	0.56
PhyloP100		-1.8
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: rs6886834; hg19: chr5-31451449;