chr5-31520127-G-A

Position:

• chr5-31520127-G-A

Variant summary

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

The NM_001382508.1(DROSHA):​c.947+996C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,702 control chromosomes in the GnomAD database, including 10,949 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 0.37 (10949 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.947+996C>T		intron_variant		ENST00000344624.8	NP_001369437.1
DROSHA	NM_001100412.2	c.947+996C>T		intron_variant			NP_001093882.1
DROSHA	NM_013235.5	c.947+996C>T		intron_variant			NP_037367.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.947+996C>T		intron_variant		5	NM_001382508.1	ENSP00000339845	P4

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56212 AN: 151582 Hom.: 10934 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.371 AC: 56275 AN: 151702 Hom.: 10949 Cov.: 32 AF XY: 0.375 AC XY: 27768 AN XY: 74142

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.355

Alfa AF: 0.241 Hom.: 693

Bravo AF: 0.373

Asia WGS AF: 0.563 AC: 1954 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.41

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: rs10461898; hg19: chr5-31520234;