chr5-31504144-A-G

Variant names:

• chr5-31504144-A-G
• rs7737174
• NM_001382508.1:c.1668+411T>C

Variant summary

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

The NM_001382508.1(DROSHA):​c.1668+411T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,034 control chromosomes in the GnomAD database, including 8,490 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 0.33 (8490 hom., cov: 32)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 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.1668+411T>C		intron	N/A	NP_001369437.1	Q9NRR4-1
	DROSHA	NM_013235.5		c.1668+411T>C		intron	N/A	NP_037367.3
	DROSHA	NM_001100412.2		c.1557+411T>C		intron	N/A	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.1668+411T>C		intron	N/A	ENSP00000339845.3	Q9NRR4-1
	DROSHA	ENST00000511367.6	TSL:1	c.1668+411T>C		intron	N/A	ENSP00000425979.2	Q9NRR4-1
	DROSHA	ENST00000513349.5	TSL:1	c.1557+411T>C		intron	N/A	ENSP00000424161.1	Q9NRR4-4

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50028 AN: 151916 Hom.: 8492 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.329 AC: 50051 AN: 152034 Hom.: 8490 Cov.: 32 AF XY: 0.330 AC XY: 24517 AN XY: 74326

African (AFR) AF: 0.289 AC: 11966 AN: 41456

American (AMR) AF: 0.353 AC: 5395 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1388 AN: 3472

East Asian (EAS) AF: 0.584 AC: 3017 AN: 5162

South Asian (SAS) AF: 0.351 AC: 1688 AN: 4812

European-Finnish (FIN) AF: 0.317 AC: 3355 AN: 10580

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22073 AN: 67970

Other (OTH) AF: 0.338 AC: 713 AN: 2108

Alfa AF: 0.331 Hom.: 23307

Bravo AF: 0.330

Asia WGS AF: 0.467 AC: 1623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.31
DANN	Benign	0.41
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7737174; hg19: chr5-31504251;