rs7719666

Positions:

• chr5-31520671-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382508.1(DROSHA):​c.947+452G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,902 control chromosomes in the GnomAD database, including 15,200 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 0.44 (15200 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DROSHA	NM_001382508.1	c.947+452G>A		intron_variant		ENST00000344624.8
DROSHA	NM_001100412.2	c.947+452G>A		intron_variant
DROSHA	NM_013235.5	c.947+452G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DROSHA	ENST00000344624.8	c.947+452G>A		intron_variant		5	NM_001382508.1	P4

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67275 AN: 151788 Hom.: 15197 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.443 AC: 67308 AN: 151902 Hom.: 15200 Cov.: 32 AF XY: 0.442 AC XY: 32818 AN XY: 74234

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.445

Alfa AF: 0.480 Hom.: 5491

Bravo AF: 0.435

Asia WGS AF: 0.326 AC: 1136 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs7719666; hg19: chr5-31520778;