5-31465128-G-A

Position:

• chr5-31465128-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.2467-785C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 152,212 control chromosomes in the GnomAD database, including 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 0.022 (190 hom., cov: 31)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.892

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]

DROSHA (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.2467-785C>T		intron_variant		ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5	c.2467-785C>T		intron_variant			NP_037367.3
DROSHA	NM_001100412.2	c.2356-785C>T		intron_variant			NP_001093882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.2467-785C>T		intron_variant		5	NM_001382508.1	ENSP00000339845.3

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3284 AN: 152094 Hom.: 187 Cov.: 31

Gnomad AFR AF: 0.00210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0397

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.0760

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00732

Gnomad OTH AF: 0.0191

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

GnomAD4 genome AF: 0.0216 AC: 3292 AN: 152212 Hom.: 190 Cov.: 31 AF XY: 0.0260 AC XY: 1931 AN XY: 74412

Gnomad4 AFR AF: 0.00209

Gnomad4 AMR AF: 0.0405

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.0760

Gnomad4 NFE AF: 0.00732

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0156 Hom.: 6

Bravo AF: 0.0208

Asia WGS AF: 0.103 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.40

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: rs10520981; hg19: chr5-31465235;