5-31486433-A-G

Variant names:

• chr5-31486433-A-G
• rs7735863
• NM_001382508.1:c.1914+58T>C

Variant summary

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

The NM_001382508.1(DROSHA):​c.1914+58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 1,550,712 control chromosomes in the GnomAD database, including 595,867 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 0.74 (45741 hom., cov: 33)
  • Exomes 𝑓: 0.88 (550126 hom.)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.1914+58T>C		intron_variant	Intron 14 of 35	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5	c.1914+58T>C		intron_variant	Intron 13 of 34		NP_037367.3
DROSHA	NM_001100412.2	c.1803+58T>C		intron_variant	Intron 13 of 34		NP_001093882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.1914+58T>C		intron_variant	Intron 14 of 35	5	NM_001382508.1	ENSP00000339845.3

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113317 AN: 152006 Hom.: 45739 Cov.: 33

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.770

GnomAD4 exome AF: 0.881 AC: 1232795 AN: 1398588 Hom.: 550126 AF XY: 0.884 AC XY: 617020 AN XY: 698088

Gnomad4 AFR exome AF: 0.396

Gnomad4 AMR exome AF: 0.823

Gnomad4 ASJ exome AF: 0.871

Gnomad4 EAS exome AF: 0.559

Gnomad4 SAS exome AF: 0.907

Gnomad4 FIN exome AF: 0.852

Gnomad4 NFE exome AF: 0.912

Gnomad4 OTH exome AF: 0.846

GnomAD4 genome AF: 0.745 AC: 113331 AN: 152124 Hom.: 45741 Cov.: 33 AF XY: 0.745 AC XY: 55415 AN XY: 74368

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.871

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.904

Gnomad4 FIN AF: 0.847

Gnomad4 NFE AF: 0.909

Gnomad4 OTH AF: 0.769

Alfa AF: 0.875 Hom.: 31147

Bravo AF: 0.723

Asia WGS AF: 0.718 AC: 2500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.55

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: rs7735863; hg19: chr5-31486540; COSMIC: COSV60772637; COSMIC: COSV60772637;