rs639174

Positions:

• chr5-31433540-C-T

Variant summary

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

The NM_001382508.1(DROSHA):​c.3043-1862G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,946 control chromosomes in the GnomAD database, including 11,272 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 0.36 (11272 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.3043-1862G>A		intron_variant		ENST00000344624.8	NP_001369437.1
DROSHA	NM_001100412.2	c.2932-1862G>A		intron_variant			NP_001093882.1
DROSHA	NM_013235.5	c.3043-1862G>A		intron_variant			NP_037367.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.3043-1862G>A		intron_variant		5	NM_001382508.1	ENSP00000339845	P4
DROSHA	ENST00000511367.6	c.3043-1862G>A		intron_variant		1		ENSP00000425979	P4
DROSHA	ENST00000513349.5	c.2932-1862G>A		intron_variant		1		ENSP00000424161	A1
DROSHA	ENST00000504133.5	n.187-1862G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54248 AN: 151828 Hom.: 11241 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.358 AC: 54330 AN: 151946 Hom.: 11272 Cov.: 32 AF XY: 0.361 AC XY: 26832 AN XY: 74250

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.353

Alfa AF: 0.268 Hom.: 7791

Bravo AF: 0.367

Asia WGS AF: 0.540 AC: 1874 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.056
DANN	Benign	0.38

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: rs639174; hg19: chr5-31433647;