rs1789502

chr18-36038869-T-Cchr18-36038869-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018170.5(RPRD1A):c.152-5032A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.993 in 152,310 control chromosomes in the GnomAD database, including 75,027 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 0.99 (75027 hom., cov: 31)
• Consequence: RPRD1A NM_018170.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634

Genes affected

RPRD1A (HGNC:25560): (regulation of nuclear pre-mRNA domain containing 1A) This gene encodes a cell-cycle and transcription regulatory protein. The encoded protein interacts with the cell cycle inhibitor cyclin-dependent kinase 4 inhibitor B and may function as a negative regulator of G(1)/S phase progression. This protein also forms homo- and hetrodimers with the protein, regulation of nuclear pre-mRNA domain-containing protein 1B, to form a scaffold that interacts with the C-terminal domain of RNA polymerase II subunit B1 and regulates several aspects of transcription. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 16. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPRD1A	NM_018170.5	c.152-5032A>G		intron_variant		ENST00000399022.9
RPRD1A	NM_001303411.2	c.43+1938A>G		intron_variant
RPRD1A	NM_001303412.2	c.43+1938A>G		intron_variant
RPRD1A	NM_001303413.2	c.152-5032A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPRD1A	ENST00000399022.9	c.152-5032A>G		intron_variant		1	NM_018170.5	P1

Frequencies

GnomAD3 genomes AF: 0.993 AC: 151053 AN: 152192 Hom.: 74969 Cov.: 31

Gnomad AFR AF: 0.975

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.996

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.995

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

GnomAD4 genome AF: 0.993 AC: 151170 AN: 152310 Hom.: 75027 Cov.: 31 AF XY: 0.993 AC XY: 73949 AN XY: 74484

Gnomad4 AFR AF: 0.975

Gnomad4 AMR AF: 0.996

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.995

Alfa AF: 0.998 Hom.: 4090

Bravo AF: 0.992

Asia WGS AF: 0.999 AC: 3473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.5
Dann	Benign	0.28

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: rs1789502; hg19: chr18-33618832;