chr5-31435520-A-C

Variant names:

• chr5-31435520-A-C
• rs4867329
• NM_001382508.1:c.3042+245T>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.3042+245T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,144 control chromosomes in the GnomAD database, including 16,135 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 0.45 (16135 hom., cov: 33)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 11 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=-0.53).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.3042+245T>G		intron_variant	Intron 25 of 35	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5	c.3042+245T>G		intron_variant	Intron 24 of 34		NP_037367.3
DROSHA	NM_001100412.2	c.2931+245T>G		intron_variant	Intron 24 of 34		NP_001093882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.3042+245T>G		intron_variant	Intron 25 of 35	5	NM_001382508.1	ENSP00000339845.3
DROSHA	ENST00000511367.6	c.3042+245T>G		intron_variant	Intron 24 of 34	1		ENSP00000425979.2
DROSHA	ENST00000513349.5	c.2931+245T>G		intron_variant	Intron 24 of 34	1		ENSP00000424161.1
DROSHA	ENST00000504133.5	n.186+245T>G		intron_variant	Intron 2 of 6	3

Frequencies

GnomAD3 genomes AF: 0.450 AC: 67955 AN: 151024 Hom.: 16121 Cov.: 33

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.450 AC: 67980 AN: 151144 Hom.: 16135 Cov.: 33 AF XY: 0.448 AC XY: 33083 AN XY: 73854

African (AFR) AF: 0.309 AC: 12661 AN: 40914

American (AMR) AF: 0.454 AC: 6931 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1484 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1247 AN: 4958

South Asian (SAS) AF: 0.467 AC: 2245 AN: 4804

European-Finnish (FIN) AF: 0.510 AC: 5356 AN: 10504

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

European-Non Finnish (NFE) AF: 0.537 AC: 36513 AN: 67942

Other (OTH) AF: 0.449 AC: 942 AN: 2096

Alfa AF: 0.504 Hom.: 75524

Bravo AF: 0.438

Asia WGS AF: 0.322 AC: 1106 AN: 3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		1.1
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: rs4867329; hg19: chr5-31435627;