20-38060491-A-G

Position:

• chr20-38060491-A-G

Variant summary

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

The NM_021215.4(RPRD1B):​c.655+971A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,058 control chromosomes in the GnomAD database, including 28,559 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 0.58 (28559 hom., cov: 32)
• Consequence: RPRD1B NM_021215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

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 = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPRD1B	NM_021215.4	c.655+971A>G		intron_variant		ENST00000373433.9	NP_067038.1
RPRD1B	XM_047440346.1	c.331+971A>G		intron_variant			XP_047296302.1
RPRD1B	XM_047440347.1	c.256+971A>G		intron_variant			XP_047296303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPRD1B	ENST00000373433.9	c.655+971A>G		intron_variant		1	NM_021215.4	ENSP00000362532.4
RPRD1B	ENST00000449186.2	c.301+971A>G		intron_variant		4		ENSP00000416420.2
RPRD1B	ENST00000462548.6	n.*342+971A>G		intron_variant		5		ENSP00000436816.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88713 AN: 151940 Hom.: 28510 Cov.: 32

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.584 AC: 88822 AN: 152058 Hom.: 28559 Cov.: 32 AF XY: 0.581 AC XY: 43161 AN XY: 74316

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.608

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.575

Alfa AF: 0.522 Hom.: 3789

Bravo AF: 0.592

Asia WGS AF: 0.623 AC: 2168 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	2.6
DANN	Benign	0.67

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: rs6022716; hg19: chr20-36688893;