chr5-31491014-G-A

Position:

• chr5-31491014-G-A

Variant summary

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

The NM_001382508.1(DROSHA):​c.1842+2193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,044 control chromosomes in the GnomAD database, including 1,189 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 0.11 (1189 hom., cov: 31)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DROSHA	NM_001382508.1	c.1842+2193C>T		intron_variant		ENST00000344624.8
DROSHA	NM_001100412.2	c.1731+2193C>T		intron_variant
DROSHA	NM_013235.5	c.1842+2193C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DROSHA	ENST00000344624.8	c.1842+2193C>T		intron_variant		5	NM_001382508.1	P4
DROSHA	ENST00000511367.6	c.1842+2193C>T		intron_variant		1		P4
DROSHA	ENST00000513349.5	c.1731+2193C>T		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16636 AN: 151928 Hom.: 1180 Cov.: 31

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.0985

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.0483

Gnomad FIN AF: 0.0717

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0658

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.110 AC: 16671 AN: 152044 Hom.: 1189 Cov.: 31 AF XY: 0.109 AC XY: 8103 AN XY: 74324

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.0981

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.0479

Gnomad4 FIN AF: 0.0717

Gnomad4 NFE AF: 0.0658

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0740 Hom.: 967

Bravo AF: 0.117

Asia WGS AF: 0.140 AC: 488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.56

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: rs6884823; hg19: chr5-31491121;