rs524138

Variant names:

• chr5-31465030-G-A
• rs524138
• NM_001382508.1:c.2467-687C>T

Variant summary

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

The NM_001382508.1(DROSHA):​c.2467-687C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 151,788 control chromosomes in the GnomAD database, including 1,422 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 0.10 (1422 hom., cov: 31)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.2467-687C>T		intron_variant	Intron 19 of 35	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5	c.2467-687C>T		intron_variant	Intron 18 of 34		NP_037367.3
DROSHA	NM_001100412.2	c.2356-687C>T		intron_variant	Intron 18 of 34		NP_001093882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.2467-687C>T		intron_variant	Intron 19 of 35	5	NM_001382508.1	ENSP00000339845.3

Frequencies

GnomAD3 genomes AF: 0.0993 AC: 15063 AN: 151670 Hom.: 1399 Cov.: 31

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.0468

Gnomad FIN AF: 0.0816

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0261

Gnomad OTH AF: 0.0784

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

GnomAD4 genome AF: 0.0997 AC: 15135 AN: 151788 Hom.: 1422 Cov.: 31 AF XY: 0.100 AC XY: 7423 AN XY: 74110

African (AFR) AF: 0.233 AC: 9650 AN: 41364

American (AMR) AF: 0.0781 AC: 1192 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3466

East Asian (EAS) AF: 0.218 AC: 1120 AN: 5132

South Asian (SAS) AF: 0.0470 AC: 226 AN: 4804

European-Finnish (FIN) AF: 0.0816 AC: 853 AN: 10458

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0261 AC: 1775 AN: 67974

Other (OTH) AF: 0.0795 AC: 168 AN: 2114

Alfa AF: 0.0497 Hom.: 2068

Bravo AF: 0.107

Asia WGS AF: 0.129 AC: 448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.87
DANN	Benign	0.71
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs524138; hg19: chr5-31465137;