chr5-31462870-G-A

Variant names:

• chr5-31462870-G-A
• rs3805500
• NM_001382508.1:c.2574+1366C>T

Variant summary

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

The NM_001382508.1(DROSHA):​c.2574+1366C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,882 control chromosomes in the GnomAD database, including 27,969 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 0.60 (27969 hom., cov: 30)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.2574+1366C>T		intron_variant	Intron 20 of 35	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5	c.2574+1366C>T		intron_variant	Intron 19 of 34		NP_037367.3
DROSHA	NM_001100412.2	c.2463+1366C>T		intron_variant	Intron 19 of 34		NP_001093882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.2574+1366C>T		intron_variant	Intron 20 of 35	5	NM_001382508.1	ENSP00000339845.3

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90715 AN: 151764 Hom.: 27967 Cov.: 30

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.597 AC: 90739 AN: 151882 Hom.: 27969 Cov.: 30 AF XY: 0.596 AC XY: 44217 AN XY: 74246

African (AFR) AF: 0.518 AC: 21451 AN: 41400

American (AMR) AF: 0.583 AC: 8892 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2091 AN: 3466

East Asian (EAS) AF: 0.196 AC: 1014 AN: 5170

South Asian (SAS) AF: 0.690 AC: 3321 AN: 4816

European-Finnish (FIN) AF: 0.611 AC: 6435 AN: 10538

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.671 AC: 45551 AN: 67916

Other (OTH) AF: 0.599 AC: 1266 AN: 2112

Alfa AF: 0.590 Hom.: 10383

Bravo AF: 0.588

Asia WGS AF: 0.430 AC: 1498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.4
DANN	Benign	0.79
PhyloP100		-0.072
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: rs3805500; hg19: chr5-31462977;