chr5-31436933-C-T

Variant names:

• chr5-31436933-C-T
• rs493760
• NM_001382508.1:c.2942+306G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382508.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	NM_001382508.1	MANE Select	c.2942+306G>A		intron	N/A	NP_001369437.1
	DROSHA	NM_013235.5		c.2942+306G>A		intron	N/A	NP_037367.3
	DROSHA	NM_001100412.2		c.2831+306G>A		intron	N/A	NP_001093882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	ENST00000344624.8	TSL:5 MANE Select	c.2942+306G>A		intron	N/A	ENSP00000339845.3
	DROSHA	ENST00000511367.6	TSL:1	c.2942+306G>A		intron	N/A	ENSP00000425979.2
	DROSHA	ENST00000513349.5	TSL:1	c.2831+306G>A		intron	N/A	ENSP00000424161.1

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

African (AFR) AF: 0.803 AC: 33344 AN: 41514

American (AMR) AF: 0.725 AC: 11086 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2270 AN: 3472

East Asian (EAS) AF: 0.795 AC: 4114 AN: 5176

South Asian (SAS) AF: 0.765 AC: 3685 AN: 4814

European-Finnish (FIN) AF: 0.722 AC: 7636 AN: 10576

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.713 AC: 48484 AN: 67984

Other (OTH) AF: 0.738 AC: 1557 AN: 2110

Alfa AF: 0.717 Hom.: 51243

Bravo AF: 0.745

Asia WGS AF: 0.779 AC: 2709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.70
PhyloP100		1.7
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: rs493760; hg19: chr5-31437040;