5-31413042-A-G

Position:

• chr5-31413042-A-G

Variant summary

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

The NM_001382508.1(DROSHA):​c.3526-2155T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,070 control chromosomes in the GnomAD database, including 4,222 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 0.23 (4222 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.3526-2155T>C		intron_variant		ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5	c.3526-2155T>C		intron_variant			NP_037367.3
DROSHA	NM_001100412.2	c.3415-2155T>C		intron_variant			NP_001093882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.3526-2155T>C		intron_variant		5	NM_001382508.1	ENSP00000339845.3
DROSHA	ENST00000511367.6	c.3526-2155T>C		intron_variant		1		ENSP00000425979.2
DROSHA	ENST00000513349.5	c.3415-2155T>C		intron_variant		1		ENSP00000424161.1
DROSHA	ENST00000511778.5	n.642-2155T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34489 AN: 151952 Hom.: 4208 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.227 AC: 34540 AN: 152070 Hom.: 4222 Cov.: 32 AF XY: 0.232 AC XY: 17237 AN XY: 74342

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.239

Alfa AF: 0.196 Hom.: 1492

Bravo AF: 0.235

Asia WGS AF: 0.411 AC: 1425 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	0.32
DANN	Benign	0.29

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: rs874332; hg19: chr5-31413149;