chr5-31409103-G-A

Variant names:

• chr5-31409103-G-A
• rs181677016
• NM_001382508.1:c.3807C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001382508.1(DROSHA):​c.3807C>T​(p.Cys1269Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,613,914 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (2 hom.)
• Consequence: DROSHA NM_001382508.1 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.451
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 5-31409103-G-A is Benign according to our data. Variant chr5-31409103-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3040208.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.451 with no splicing effect.
• BS2: High AC in GnomAd4 at 30 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382508.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	NM_001382508.1	MANE Select	c.3807C>T	p.Cys1269Cys	synonymous	Exon 33 of 36	NP_001369437.1	Q9NRR4-1
	DROSHA	NM_013235.5		c.3807C>T	p.Cys1269Cys	synonymous	Exon 32 of 35	NP_037367.3
	DROSHA	NM_001100412.2		c.3696C>T	p.Cys1232Cys	synonymous	Exon 32 of 35	NP_001093882.1	Q9NRR4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	ENST00000344624.8	TSL:5 MANE Select	c.3807C>T	p.Cys1269Cys	synonymous	Exon 33 of 36	ENSP00000339845.3	Q9NRR4-1
	DROSHA	ENST00000511367.6	TSL:1	c.3807C>T	p.Cys1269Cys	synonymous	Exon 32 of 35	ENSP00000425979.2	Q9NRR4-1
	DROSHA	ENST00000513349.5	TSL:1	c.3696C>T	p.Cys1232Cys	synonymous	Exon 32 of 35	ENSP00000424161.1	Q9NRR4-4

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000333 AC: 83 AN: 248930 AF XY: 0.000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00368

Gnomad FIN exome AF: 0.000232

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000153 AC: 224 AN: 1461596 Hom.: 2 Cov.: 31 AF XY: 0.000184 AC XY: 134 AN XY: 727086

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00388 AC: 154 AN: 39686

South Asian (SAS) AF: 0.000464 AC: 40 AN: 86256

European-Finnish (FIN) AF: 0.000243 AC: 13 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111792

Other (OTH) AF: 0.000149 AC: 9 AN: 60372

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19 AN XY: 74478

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000854 Hom.: 0

Bravo AF: 0.000257

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DROSHA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.2
DANN	Benign	0.67
PhyloP100		0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs181677016; hg19: chr5-31409210; COSMIC: COSV60783292; COSMIC: COSV60783292;