chr5-31430775-T-C

Variant names:

• chr5-31430775-T-C
• rs9292427
• NM_001382508.1:c.3145+801A>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.3145+801A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,034 control chromosomes in the GnomAD database, including 16,007 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 0.44 (16007 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 4 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=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.3145+801A>G		intron_variant	Intron 26 of 35	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5	c.3145+801A>G		intron_variant	Intron 25 of 34		NP_037367.3
DROSHA	NM_001100412.2	c.3034+801A>G		intron_variant	Intron 25 of 34		NP_001093882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.3145+801A>G		intron_variant	Intron 26 of 35	5	NM_001382508.1	ENSP00000339845.3
DROSHA	ENST00000511367.6	c.3145+801A>G		intron_variant	Intron 25 of 34	1		ENSP00000425979.2
DROSHA	ENST00000513349.5	c.3034+801A>G		intron_variant	Intron 25 of 34	1		ENSP00000424161.1
DROSHA	ENST00000504133.5	n.289+801A>G		intron_variant	Intron 3 of 6	3

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67547 AN: 151916 Hom.: 15995 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.444 AC: 67569 AN: 152034 Hom.: 16007 Cov.: 32 AF XY: 0.443 AC XY: 32901 AN XY: 74342

African (AFR) AF: 0.297 AC: 12308 AN: 41462

American (AMR) AF: 0.453 AC: 6918 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1484 AN: 3466

East Asian (EAS) AF: 0.241 AC: 1246 AN: 5172

South Asian (SAS) AF: 0.462 AC: 2230 AN: 4828

European-Finnish (FIN) AF: 0.507 AC: 5359 AN: 10576

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36481 AN: 67936

Other (OTH) AF: 0.445 AC: 942 AN: 2116

Alfa AF: 0.510 Hom.: 10254

Bravo AF: 0.436

Asia WGS AF: 0.316 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		0.14
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: rs9292427; hg19: chr5-31430882;