NM_001382508.1:c.2574+4908A>C

Variant names:

• chr5-31459328-T-G
• rs640831
• NM_001382508.1:c.2574+4908A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382508.1(DROSHA):​c.2574+4908A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 150,474 control chromosomes in the GnomAD database, including 37,240 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 0.70 (37240 hom., cov: 26)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 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.2574+4908A>C		intron	N/A	NP_001369437.1
	DROSHA	NM_013235.5		c.2574+4908A>C		intron	N/A	NP_037367.3
	DROSHA	NM_001100412.2		c.2463+4908A>C		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.2574+4908A>C		intron	N/A	ENSP00000339845.3
	DROSHA	ENST00000511367.6	TSL:1	c.2574+4908A>C		intron	N/A	ENSP00000425979.2
	DROSHA	ENST00000513349.5	TSL:1	c.2463+4908A>C		intron	N/A	ENSP00000424161.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 105389 AN: 150356 Hom.: 37195 Cov.: 26

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.683

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

GnomAD4 genome AF: 0.701 AC: 105486 AN: 150474 Hom.: 37240 Cov.: 26 AF XY: 0.700 AC XY: 51345 AN XY: 73298

African (AFR) AF: 0.759 AC: 31048 AN: 40918

American (AMR) AF: 0.666 AC: 10017 AN: 15040

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2205 AN: 3466

East Asian (EAS) AF: 0.422 AC: 2122 AN: 5034

South Asian (SAS) AF: 0.737 AC: 3504 AN: 4752

European-Finnish (FIN) AF: 0.700 AC: 7156 AN: 10224

Middle Eastern (MID) AF: 0.643 AC: 184 AN: 286

European-Non Finnish (NFE) AF: 0.697 AC: 47249 AN: 67752

Other (OTH) AF: 0.682 AC: 1429 AN: 2096

Alfa AF: 0.632 Hom.: 1939

Bravo AF: 0.697

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.31
PhyloP100		-0.55
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: rs640831; hg19: chr5-31459435;