rs4904670

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRDE2	NM_017970.4	c.1005+69G>C		intron_variant		ENST00000354366.8	NP_060440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRDE2	ENST00000354366.8	c.1005+69G>C		intron_variant		1	NM_017970.4	ENSP00000346335.3
NRDE2	ENST00000553409.5	n.*530+69G>C		intron_variant		1		ENSP00000451025.1
NRDE2	ENST00000556189.5	n.570+69G>C		intron_variant		1		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

Gnomad4 AFR exome AF: 0.868

Gnomad4 AMR exome AF: 0.993

Gnomad4 ASJ exome AF: 0.998

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.986

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.991

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

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.983

Gnomad4 ASJ AF: 0.998

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.985

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.975

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs4904670; hg19: chr14-90770210;