rs11748548

chr5-31492281-A-Gchr5-31492281-A-T

Variant summary

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

The NM_001382508.1(DROSHA):c.1842+926T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 152,056 control chromosomes in the GnomAD database, including 66,509 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 0.93 (66509 hom., cov: 33)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DROSHA	NM_001382508.1	c.1842+926T>C		intron_variant		ENST00000344624.8
DROSHA	NM_001100412.2	c.1731+926T>C		intron_variant
DROSHA	NM_013235.5	c.1842+926T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DROSHA	ENST00000344624.8	c.1842+926T>C		intron_variant		5	NM_001382508.1	P4
DROSHA	ENST00000511367.6	c.1842+926T>C		intron_variant		1		P4
DROSHA	ENST00000513349.5	c.1731+926T>C		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.934 AC: 141897 AN: 151938 Hom.: 66491 Cov.: 33

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.977

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.978

Gnomad OTH AF: 0.948

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

GnomAD4 genome AF: 0.934 AC: 141957 AN: 152056 Hom.: 66509 Cov.: 33 AF XY: 0.931 AC XY: 69180 AN XY: 74328

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.935

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.977

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.978

Gnomad4 OTH AF: 0.946

Alfa AF: 0.953 Hom.: 20681

Bravo AF: 0.930

Asia WGS AF: 0.885 AC: 3077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.84
Dann	Benign	0.61

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: rs11748548; hg19: chr5-31492388;