rs1260457

Variant names:

• chr1-150374898-G-A
• rs1260457
• NM_015203.5:c.205+9979G>A

Variant summary

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

The NM_015203.5(RPRD2):​c.205+9979G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,722 control chromosomes in the GnomAD database, including 27,752 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 0.60 (27752 hom., cov: 30)
• Consequence: RPRD2 NM_015203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 3 publications found

Genes affected

RPRD2 (HGNC:29039): (regulation of nuclear pre-mRNA domain containing 2) Predicted to enable RNA polymerase II complex binding activity. Predicted to be involved in mRNA 3'-end processing. Part of RNA polymerase II, holoenzyme. [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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015203.5. 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
	RPRD2	NM_015203.5	MANE Select	c.205+9979G>A		intron	N/A	NP_056018.2	Q5VT52-1
	RPRD2	NM_001297674.2		c.205+9979G>A		intron	N/A	NP_001284603.1	Q5VT52-3
	RPRD2	NM_001387119.1		c.205+9979G>A		intron	N/A	NP_001374048.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPRD2	ENST00000369068.5	TSL:1 MANE Select	c.205+9979G>A		intron	N/A	ENSP00000358064.4	Q5VT52-1
	RPRD2	ENST00000401000.8	TSL:1	c.205+9979G>A		intron	N/A	ENSP00000383785.4	Q5VT52-3
	RPRD2	ENST00000879565.1		c.205+9979G>A		intron	N/A	ENSP00000549624.1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90848 AN: 151604 Hom.: 27723 Cov.: 30

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.599 AC: 90924 AN: 151722 Hom.: 27752 Cov.: 30 AF XY: 0.592 AC XY: 43920 AN XY: 74128

African (AFR) AF: 0.649 AC: 26844 AN: 41356

American (AMR) AF: 0.505 AC: 7703 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2204 AN: 3462

East Asian (EAS) AF: 0.300 AC: 1545 AN: 5152

South Asian (SAS) AF: 0.415 AC: 1991 AN: 4802

European-Finnish (FIN) AF: 0.658 AC: 6903 AN: 10496

Middle Eastern (MID) AF: 0.500 AC: 145 AN: 290

European-Non Finnish (NFE) AF: 0.617 AC: 41884 AN: 67906

Other (OTH) AF: 0.572 AC: 1204 AN: 2106

Alfa AF: 0.617 Hom.: 6066

Bravo AF: 0.590

Asia WGS AF: 0.428 AC: 1489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.79
DANN	Benign	0.82
PhyloP100		-1.5
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: rs1260457; hg19: chr1-150347374;