chr5-31446609-T-C

Position:

• chr5-31446609-T-C

Variant summary

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

The NM_001382508.1(DROSHA):​c.2882+1938A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 150,364 control chromosomes in the GnomAD database, including 1,661 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 0.13 (1661 hom., cov: 29)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.2882+1938A>G		intron_variant		ENST00000344624.8	NP_001369437.1
DROSHA	NM_001100412.2	c.2771+1938A>G		intron_variant			NP_001093882.1
DROSHA	NM_013235.5	c.2882+1938A>G		intron_variant			NP_037367.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.2882+1938A>G		intron_variant		5	NM_001382508.1	ENSP00000339845	P4
DROSHA	ENST00000511367.6	c.2882+1938A>G		intron_variant		1		ENSP00000425979	P4
DROSHA	ENST00000513349.5	c.2771+1938A>G		intron_variant		1		ENSP00000424161	A1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 18863 AN: 150252 Hom.: 1650 Cov.: 29

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.0712

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.126 AC: 18899 AN: 150364 Hom.: 1661 Cov.: 29 AF XY: 0.123 AC XY: 9053 AN XY: 73380

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.0970

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.0321

Gnomad4 FIN AF: 0.0712

Gnomad4 NFE AF: 0.0700

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0823 Hom.: 510

Bravo AF: 0.136

Asia WGS AF: 0.135 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.8
DANN	Benign	0.71

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: rs10067066; hg19: chr5-31446716;