chr5-31514020-C-T

Variant names:

• chr5-31514020-C-T
• rs17409275
• NM_001382508.1:c.1290+968G>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.1290+968G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,738 control chromosomes in the GnomAD database, including 10,152 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 0.34 (10152 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.1290+968G>A		intron_variant	Intron 8 of 35	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5	c.1290+968G>A		intron_variant	Intron 7 of 34		NP_037367.3
DROSHA	NM_001100412.2	c.1179+968G>A		intron_variant	Intron 7 of 34		NP_001093882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.1290+968G>A		intron_variant	Intron 8 of 35	5	NM_001382508.1	ENSP00000339845.3
DROSHA	ENST00000511367.6	c.1290+968G>A		intron_variant	Intron 7 of 34	1		ENSP00000425979.2
DROSHA	ENST00000513349.5	c.1179+968G>A		intron_variant	Intron 7 of 34	1		ENSP00000424161.1
DROSHA	ENST00000512076.1	c.573+968G>A		intron_variant	Intron 2 of 6	1		ENSP00000422745.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51439 AN: 151620 Hom.: 10156 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.0396

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.339 AC: 51433 AN: 151738 Hom.: 10152 Cov.: 32 AF XY: 0.337 AC XY: 24982 AN XY: 74122

African (AFR) AF: 0.152 AC: 6316 AN: 41460

American (AMR) AF: 0.366 AC: 5567 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1139 AN: 3464

East Asian (EAS) AF: 0.0395 AC: 204 AN: 5168

South Asian (SAS) AF: 0.385 AC: 1856 AN: 4816

European-Finnish (FIN) AF: 0.421 AC: 4414 AN: 10490

Middle Eastern (MID) AF: 0.306 AC: 88 AN: 288

European-Non Finnish (NFE) AF: 0.452 AC: 30644 AN: 67814

Other (OTH) AF: 0.352 AC: 742 AN: 2106

Alfa AF: 0.403 Hom.: 25637

Bravo AF: 0.324

Asia WGS AF: 0.212 AC: 740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.81
DANN	Benign	0.42
PhyloP100		-1.1
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: rs17409275; hg19: chr5-31514127;