rs4904670

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-90303866-C-G
• chr14-90303866-C-T

Variant summary

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

The NM_017970.4(NRDE2):​c.1005+69G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,381,298 control chromosomes in the GnomAD database, including 679,816 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 0.96 (70885 hom., cov: 32)
  • Exomes 𝑓: 1.0 (608931 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

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>C		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>C		intron	N/A	ENSP00000346335.3
	NRDE2	ENST00000553409.5	TSL:1	n.*530+69G>C		intron	N/A	ENSP00000451025.1
	NRDE2	ENST00000556189.5	TSL:1	n.570+69G>C		intron	N/A	ENSP00000452107.1

Frequencies

GnomAD3 genomes AF: 0.964 AC: 146640 AN: 152168 Hom.: 70842 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.983

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.985

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.975

GnomAD4 exome AF: 0.995 AC: 1223166 AN: 1229012 Hom.: 608931 AF XY: 0.995 AC XY: 605635 AN XY: 608552

African (AFR) AF: 0.868 AC: 24095 AN: 27748

American (AMR) AF: 0.993 AC: 30360 AN: 30564

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 19281 AN: 19314

East Asian (EAS) AF: 1.00 AC: 38248 AN: 38250

South Asian (SAS) AF: 0.986 AC: 67684 AN: 68634

European-Finnish (FIN) AF: 1.00 AC: 47905 AN: 47908

Middle Eastern (MID) AF: 0.991 AC: 4271 AN: 4310

European-Non Finnish (NFE) AF: 0.999 AC: 940062 AN: 940568

Other (OTH) AF: 0.991 AC: 51260 AN: 51716

GnomAD4 genome AF: 0.964 AC: 146742 AN: 152286 Hom.: 70885 Cov.: 32 AF XY: 0.964 AC XY: 71801 AN XY: 74454

African (AFR) AF: 0.878 AC: 36448 AN: 41530

American (AMR) AF: 0.983 AC: 15041 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 3464 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5172 AN: 5174

South Asian (SAS) AF: 0.985 AC: 4761 AN: 4834

European-Finnish (FIN) AF: 1.00 AC: 10613 AN: 10614

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67982 AN: 68046

Other (OTH) AF: 0.975 AC: 2059 AN: 2112

Alfa AF: 0.991 Hom.: 3494

Bravo AF: 0.957

Asia WGS AF: 0.983 AC: 3419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.37
PhyloP100		-1.0
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: rs4904670; hg19: chr14-90770210;