rs11748548

Variant names:

• chr5-31492281-A-G
• rs11748548
• NM_001382508.1:c.1842+926T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-31492281-A-G
• chr5-31492281-A-T

Variant summary

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

The NM_013235.5(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_013235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013235.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	NM_001382508.1	MANE Select	c.1842+926T>C		intron	N/A	NP_001369437.1
	DROSHA	NM_013235.5		c.1842+926T>C		intron	N/A	NP_037367.3
	DROSHA	NM_001100412.2		c.1731+926T>C		intron	N/A	NP_001093882.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	ENST00000344624.8	TSL:5 MANE Select	c.1842+926T>C		intron	N/A	ENSP00000339845.3
	DROSHA	ENST00000511367.6	TSL:1	c.1842+926T>C		intron	N/A	ENSP00000425979.2
	DROSHA	ENST00000513349.5	TSL:1	c.1731+926T>C		intron	N/A	ENSP00000424161.1

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

African (AFR) AF: 0.872 AC: 36166 AN: 41458

American (AMR) AF: 0.935 AC: 14311 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3392 AN: 3470

East Asian (EAS) AF: 0.781 AC: 4031 AN: 5160

South Asian (SAS) AF: 0.977 AC: 4711 AN: 4824

European-Finnish (FIN) AF: 0.919 AC: 9693 AN: 10546

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.978 AC: 66477 AN: 67980

Other (OTH) AF: 0.946 AC: 1998 AN: 2112

Alfa AF: 0.953 Hom.: 25955

Bravo AF: 0.930

Asia WGS AF: 0.885 AC: 3077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.84
DANN	Benign	0.61
PhyloP100		-0.35
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: rs11748548; hg19: chr5-31492388;