rs6023059

chr20-38109369-T-C

Variant summary

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

The ENST00000614670.1(RPRD1B):c.176-17928T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,138 control chromosomes in the GnomAD database, including 28,982 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 0.59 (28982 hom., cov: 32)
• Consequence: RPRD1B ENST00000614670.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750

Genes affected

RPRD1B (HGNC:16209): (regulation of nuclear pre-mRNA domain containing 1B) Enables RNA polymerase II complex binding activity and identical protein binding activity. Involved in positive regulation of cell population proliferation; regulation of cell cycle process; and regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of RNA polymerase II, holoenzyme. [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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPRD1B	ENST00000614670.1	c.176-17928T>C		intron_variant		3
RPRD1B	ENST00000618318.1	n.256-15401T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89147 AN: 152020 Hom.: 28933 Cov.: 32

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.587 AC: 89255 AN: 152138 Hom.: 28982 Cov.: 32 AF XY: 0.583 AC XY: 43315 AN XY: 74356

Gnomad4 AFR AF: 0.883

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.582

Alfa AF: 0.524 Hom.: 3580

Bravo AF: 0.595

Asia WGS AF: 0.622 AC: 2167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.8
Dann	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6023059; hg19: chr20-36737771;