14-90303866-C-T

Variant names:

• chr14-90303866-C-T
• rs4904670
• NM_017970.4:c.1005+69G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017970.4(NRDE2):​c.1005+69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NRDE2 NM_017970.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 6 publications found

Genes affected

NRDE2 (HGNC:20186): (NRDE-2, necessary for RNA interference, domain containing) Involved in several processes, including RNA splicing; negative regulation of RNA catabolic process; and positive regulation of RNA export from nucleus. Located in nuclear speck and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017970.4. 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
	NRDE2	NM_017970.4	MANE Select	c.1005+69G>A		intron	N/A	NP_060440.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRDE2	ENST00000354366.8	TSL:1 MANE Select	c.1005+69G>A		intron	N/A	ENSP00000346335.3
	NRDE2	ENST00000553409.5	TSL:1	n.*530+69G>A		intron	N/A	ENSP00000451025.1
	NRDE2	ENST00000556189.5	TSL:1	n.570+69G>A		intron	N/A	ENSP00000452107.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 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: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000114 AC: 14 AN: 1229044 Hom.: 0 AF XY: 0.0000131 AC XY: 8 AN XY: 608574

African (AFR) AF: 0.00 AC: 0 AN: 27766

American (AMR) AF: 0.00 AC: 0 AN: 30564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19314

East Asian (EAS) AF: 0.00 AC: 0 AN: 38250

South Asian (SAS) AF: 0.00 AC: 0 AN: 68640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47908

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4310

European-Non Finnish (NFE) AF: 0.0000149 AC: 14 AN: 940574

Other (OTH) AF: 0.00 AC: 0 AN: 51718

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74330

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68054

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 3494

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.38
DANN	Benign	0.77
PhyloP100		-1.0

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: rs4904670; hg19: chr14-90770210;