rs2241337

Variant names:

• chr5-31409145-A-G
• rs2241337
• NM_001382508.1:c.3765T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-31409145-A-G
• chr5-31409145-A-C
• chr5-31409145-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001382508.1(DROSHA):​c.3765T>C​(p.Asn1255Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,613,412 control chromosomes in the GnomAD database, including 39,675 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.23 (4378 hom., cov: 32)
  • Exomes 𝑓: 0.21 (35297 hom.)
• Consequence: DROSHA NM_001382508.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.87
• Publications: 18 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 5-31409145-A-G is Benign according to our data. Variant chr5-31409145-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060031.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.87 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

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.3765T>C	p.Asn1255Asn	synonymous	Exon 33 of 36	NP_001369437.1	Q9NRR4-1
	DROSHA	NM_013235.5		c.3765T>C	p.Asn1255Asn	synonymous	Exon 32 of 35	NP_037367.3
	DROSHA	NM_001100412.2		c.3654T>C	p.Asn1218Asn	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.3765T>C	p.Asn1255Asn	synonymous	Exon 33 of 36	ENSP00000339845.3	Q9NRR4-1
	DROSHA	ENST00000511367.6	TSL:1	c.3765T>C	p.Asn1255Asn	synonymous	Exon 32 of 35	ENSP00000425979.2	Q9NRR4-1
	DROSHA	ENST00000513349.5	TSL:1	c.3654T>C	p.Asn1218Asn	synonymous	Exon 32 of 35	ENSP00000424161.1	Q9NRR4-4

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35183 AN: 152008 Hom.: 4363 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.234

GnomAD2 exomes AF: 0.248 AC: 61656 AN: 248404 AF XY: 0.247

Gnomad AFR exome AF: 0.259

Gnomad AMR exome AF: 0.316

Gnomad ASJ exome AF: 0.279

Gnomad EAS exome AF: 0.464

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.209 AC: 305933 AN: 1461286 Hom.: 35297 Cov.: 33 AF XY: 0.212 AC XY: 153783 AN XY: 726922

African (AFR) AF: 0.264 AC: 8831 AN: 33468

American (AMR) AF: 0.312 AC: 13942 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 7099 AN: 26118

East Asian (EAS) AF: 0.484 AC: 19188 AN: 39666

South Asian (SAS) AF: 0.311 AC: 26836 AN: 86206

European-Finnish (FIN) AF: 0.197 AC: 10491 AN: 53376

Middle Eastern (MID) AF: 0.287 AC: 1657 AN: 5768

European-Non Finnish (NFE) AF: 0.183 AC: 203986 AN: 1111662

Other (OTH) AF: 0.230 AC: 13903 AN: 60358

GnomAD4 genome AF: 0.232 AC: 35236 AN: 152126 Hom.: 4378 Cov.: 32 AF XY: 0.237 AC XY: 17601 AN XY: 74352

African (AFR) AF: 0.255 AC: 10577 AN: 41494

American (AMR) AF: 0.279 AC: 4260 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3470

East Asian (EAS) AF: 0.463 AC: 2387 AN: 5158

South Asian (SAS) AF: 0.316 AC: 1524 AN: 4822

European-Finnish (FIN) AF: 0.218 AC: 2305 AN: 10576

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12355 AN: 67996

Other (OTH) AF: 0.237 AC: 501 AN: 2110

Alfa AF: 0.204 Hom.: 8948

Bravo AF: 0.238

Asia WGS AF: 0.409 AC: 1419 AN: 3476

EpiCase AF: 0.188

EpiControl AF: 0.196

ClinVar

ClinVar submissions

Significance: 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	-0.55
CADD	Benign	7.0
DANN	Benign	0.89
PhyloP100		2.9
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2241337; hg19: chr5-31409252; COSMIC: COSV60773938; COSMIC: COSV60773938;