rs3805500

Positions:

• chr5-31462870-G-A

Variant summary

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

The NM_001382508.1(DROSHA):​c.2574+1366C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,882 control chromosomes in the GnomAD database, including 27,969 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 0.60 (27969 hom., cov: 30)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DROSHA	NM_001382508.1	c.2574+1366C>T		intron_variant		ENST00000344624.8
DROSHA	NM_001100412.2	c.2463+1366C>T		intron_variant
DROSHA	NM_013235.5	c.2574+1366C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DROSHA	ENST00000344624.8	c.2574+1366C>T		intron_variant		5	NM_001382508.1	P4

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90715 AN: 151764 Hom.: 27967 Cov.: 30

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.597 AC: 90739 AN: 151882 Hom.: 27969 Cov.: 30 AF XY: 0.596 AC XY: 44217 AN XY: 74246

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.599

Alfa AF: 0.633 Hom.: 4293

Bravo AF: 0.588

Asia WGS AF: 0.430 AC: 1498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.4
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3805500; hg19: chr5-31462977;