5-31409008-T-C

Variant names:

• chr5-31409008-T-C
• rs644236
• NM_001382508.1:c.3854+48A>G

Variant summary

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

The NM_001382508.1(DROSHA):​c.3854+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,559,842 control chromosomes in the GnomAD database, including 63,483 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 0.35 (11711 hom., cov: 32)
  • Exomes 𝑓: 0.25 (51772 hom.)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 17 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.3854+48A>G		intron_variant	Intron 33 of 35	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5	c.3854+48A>G		intron_variant	Intron 32 of 34		NP_037367.3
DROSHA	NM_001100412.2	c.3743+48A>G		intron_variant	Intron 32 of 34		NP_001093882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.3854+48A>G		intron_variant	Intron 33 of 35	5	NM_001382508.1	ENSP00000339845.3

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53293 AN: 151860 Hom.: 11678 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.330

GnomAD2 exomes AF: 0.312 AC: 70573 AN: 226424 AF XY: 0.305

Gnomad AFR exome AF: 0.603

Gnomad AMR exome AF: 0.344

Gnomad ASJ exome AF: 0.302

Gnomad EAS exome AF: 0.664

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.246 AC: 345634 AN: 1407864 Hom.: 51772 Cov.: 22 AF XY: 0.248 AC XY: 173632 AN XY: 701080

African (AFR) AF: 0.612 AC: 19671 AN: 32142

American (AMR) AF: 0.341 AC: 14045 AN: 41206

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 7347 AN: 24694

East Asian (EAS) AF: 0.711 AC: 27928 AN: 39300

South Asian (SAS) AF: 0.370 AC: 30062 AN: 81176

European-Finnish (FIN) AF: 0.254 AC: 13329 AN: 52556

Middle Eastern (MID) AF: 0.329 AC: 1822 AN: 5532

European-Non Finnish (NFE) AF: 0.200 AC: 214737 AN: 1072892

Other (OTH) AF: 0.286 AC: 16693 AN: 58366

GnomAD4 genome AF: 0.351 AC: 53378 AN: 151978 Hom.: 11711 Cov.: 32 AF XY: 0.356 AC XY: 26480 AN XY: 74288

African (AFR) AF: 0.589 AC: 24372 AN: 41394

American (AMR) AF: 0.328 AC: 5009 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1108 AN: 3470

East Asian (EAS) AF: 0.670 AC: 3445 AN: 5144

South Asian (SAS) AF: 0.380 AC: 1832 AN: 4824

European-Finnish (FIN) AF: 0.272 AC: 2879 AN: 10572

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.201 AC: 13670 AN: 67984

Other (OTH) AF: 0.335 AC: 707 AN: 2110

Alfa AF: 0.277 Hom.: 4274

Bravo AF: 0.368

Asia WGS AF: 0.539 AC: 1872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.58
PhyloP100		0.058
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs644236; hg19: chr5-31409115;