rs2279797

Variant names:

• chr5-31427921-C-T
• rs2279797
• NM_001382508.1:c.3216+1554G>A

Variant summary

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

The NM_001382508.1(DROSHA):​c.3216+1554G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,152 control chromosomes in the GnomAD database, including 2,513 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 0.17 (2513 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.3216+1554G>A		intron_variant	Intron 27 of 35	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5	c.3216+1554G>A		intron_variant	Intron 26 of 34		NP_037367.3
DROSHA	NM_001100412.2	c.3105+1554G>A		intron_variant	Intron 26 of 34		NP_001093882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.3216+1554G>A		intron_variant	Intron 27 of 35	5	NM_001382508.1	ENSP00000339845.3

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26586 AN: 152034 Hom.: 2504 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.175 AC: 26625 AN: 152152 Hom.: 2513 Cov.: 32 AF XY: 0.178 AC XY: 13240 AN XY: 74382

African (AFR) AF: 0.161 AC: 6680 AN: 41504

American (AMR) AF: 0.222 AC: 3386 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3470

East Asian (EAS) AF: 0.313 AC: 1618 AN: 5172

South Asian (SAS) AF: 0.212 AC: 1020 AN: 4822

European-Finnish (FIN) AF: 0.160 AC: 1693 AN: 10580

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10811 AN: 68016

Other (OTH) AF: 0.180 AC: 379 AN: 2110

Alfa AF: 0.167 Hom.: 9289

Bravo AF: 0.176

Asia WGS AF: 0.328 AC: 1136 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.48
PhyloP100		0.60
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: rs2279797; hg19: chr5-31428028;