rs493760

Positions:

• chr5-31436933-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001382508.1(DROSHA):​c.2942+306G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,142 control chromosomes in the GnomAD database, including 42,190 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 0.74 (42190 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DROSHA	NM_001382508.1	c.2942+306G>A		intron_variant		ENST00000344624.8
DROSHA	NM_001100412.2	c.2831+306G>A		intron_variant
DROSHA	NM_013235.5	c.2942+306G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DROSHA	ENST00000344624.8	c.2942+306G>A		intron_variant		5	NM_001382508.1	P4
DROSHA	ENST00000511367.6	c.2942+306G>A		intron_variant		1		P4
DROSHA	ENST00000513349.5	c.2831+306G>A		intron_variant		1		A1
DROSHA	ENST00000504133.5	n.86+306G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.743 AC: 113018 AN: 152024 Hom.: 42160 Cov.: 32

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.743 AC: 113095 AN: 152142 Hom.: 42190 Cov.: 32 AF XY: 0.744 AC XY: 55351 AN XY: 74370

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.738

Alfa AF: 0.715 Hom.: 39376

Bravo AF: 0.745

Asia WGS AF: 0.779 AC: 2709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.70

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: rs493760; hg19: chr5-31437040;